Scientific Committee on Consumer Products
SCCP
OPINION ON
PHTHALATES IN COSMETIC PRODUCTS
The SCCP adopted this opinion at its 11th plenary meeting of 21 March 2007
About the Scientific Committee s
Three independent non-food Scientific Committees provide the Commission with the
scientific advice it needs when preparing policy and proposals relating to consumer safety, public health and the environment. The Committees also draw the Commission's attention
to the new or emerging problems which may pose an actual or potential threat.
They are: the Scientific Committee on Consumer Products (SCCP), the Scientific Committee on Health and Environmental Risks (SCHER) and the Scientific Committee on Emerging and Newly Identified Health Risks (SCENIHR) and are made up of external experts.
In addition, the Commission relies upon the work of the European Food Safety Authority
(EFSA), the European Medicines Evaluation Agency (EMEA), the European Centre for Disease prevention and Control (ECDC) and the European Chemicals Agency (ECHA).
SCCP
Questions concerning the safety of consumer products (non-food products intended for the consumer).
In particular, the Committee addresses questions related to the safety and allergenic properties of cosmetic products and ingredients with respect to their impact on consumer health, toys, textiles, clothing, personal care products, domestic products such as detergents and consumer services such as tattooing.
Scientific Committee members
Claire Chambers, Gisela Degen, Ruta Dubakiene, Ramon Grimalt, Bozena Jazwiec-Kanyion, Vassilios Kapoulas, Jean Krutmann, Carola Lidén, Jean-Paul Marty, Thomas Platzek, Suresh Chandra Rastogi, Jean Revuz, Vera Rogiers, Tore Sanner, Günter Speit, Jacqueline Van Engelen, Ian White
Contact:
European Commission
Health & Consumer Protection DG
Directorate C: Public Health and Risk Assessment
Unit C7 - Risk Assessment
Office: B232 B-1049 Brussels
Sanco-Sc6-Secretariat@ec.europa.eu
? European Commission 2007
(ISSN)
The opinions of the Scientific Committees present the views of the independent scientists who are members of the committees. They do not necessarily reflect the views of the European Commission. The opinions are published by the European Commission in their original language only.
http://ec.europa.eu/health/ph_risk/risk_en.htm
ACKNOWLEDGMENTS
Dr. C. Chambers (rapporteur)
Prof. G. Degen
Dr. B. Jazwiec-Kanyion
Prof. V. Kapoulas
Prof. C. Lidén
Prof. J.-P. Marty
Prof. T. Platzek
Dr. S.C. Rastogi
Prof. J. Revuz
Prof. V. Rogiers
Prof. T. Sanner (chairman)
Dr. J. van Engelen
Dr. I.R. White
Keywords: SCCP, scientific opinion, phthalates
Opinion to be cited as: Opinion of the SCCP on phthalates in cosmetic products
TABLE OF CONTENTS
ACKNOWLEDGMENTS (3)
1.BACKGROUND (5)
2.TERMS OF REFERENCE (7)
(8)
3.OPINION
4.CONCLUSION (17)
5.MINORITY OPINION (18)
6.REFERENCES (18)
1.BACKGROUND
1.1 Greenpeace investigation
In February 2005 Greenpeace released An Investigation of Chemicals in Perfumes.
In the investigation inter alia the presence of 10 different phthalates were examined.
Phthalates were found in 35 out of 36 investigated perfumes.
One phthalate (DOP) out of the ten analysed for was not found in any of the products.
For 7 out of the ten phthalates that were analysed for, they were found, when present at
all, in such small amounts that they probably are not used intentionally as ingredients in the
perfumes, but rather are present as traces and/or impurities.
One phthalate, dimethyl phthalate (DMP), out of the ten analysed for, was measured in a
concentration as high as 2982 mg/kg or 0.3% DMP. COLIPA has formerly in a letter dated
the 29th November 2002 stated that “since there is no intentional use of DMP, BBzP (Butyl
benzyl phthalate) and DEHP (diethylhexyl phthalate) as cosmetic ingredients, COLIPA is not
in a position to provide detailed safety dossier on theses substances.” Names in brackets
have been added. Whether dimethyl phthalate found in the investigation actually is used as
a cosmetic ingredient, a fragrance ingredient or is present as an impurity is questionable.
And finally for the last phthalate (DEP) out of the ten analysed for, the Scientific Committee
on Cosmetics and Non-Food Products (SCCNFP) has expressed on its 20th plenary meeting
the 4th June 2002 a positive opinion (SCCNFP/411/01) on the safe use of diethyl phthalate
(DEP) in Cosmetics. This positive opinion was confirmed by the SCCNFP at its 26th plenary
meeting the 9th December 2003. This phthalate is normally used either as a denaturant for
ethanol or as a solvent in perfumes. It was present at the highest concentrations and in
most of the perfumes. The highest measured concentration for this phthalate was 22.299
mg/kg or 2.23%.
An overview of the phthalates analysed for, their status and the highest measured
concentration are given in the table below:
Name Status
Highest
concentration in
mg/kg
2982
di-methyl phthalate (DMP) No safety dossier submitted. So far not evaluated at
EU level
di-ethyl phthalate (DEP) Positive opinion SCCNFP. CICADS 52, 2003 (WHO)* 22299
38
di-isobutyl phthalate (DIBP) So far not evaluated at EU level (IUCLID Chemical
Data Sheet exists)
14
di-n-butyl phthalate (DBP) Banned under the Cosmetics Directive as CMR-
substance. EFSA Scientific opinion. Evaluated under
the Existing Chemicals Legislation, Council
Regulation 793/93/EEC. RAR and Opinion by the
CSTEE available.
110
benzylbutyl phthalate (BBP) Banned under the Cosmetics Directive as CMR-
substance. EFSA Scientific opinion. Evaluated under
the Existing Chemicals Legislation, Council
Regulation 793/93/EEC. RAR and Opinion by the
SCHER available.
3
di-cyclohexyl phthalate (DCHP) So far not evaluated at EU level (IUCLID Chemical
Data Sheet exists)
Name Status
Highest
concentration in
mg/kg
di-(2-ethylhexyl) phthalate (DEHP) Banned under the Cosmetics Directive as CMR-
substance. EFSA Scientific opinion. Evaluated under
the Existing Chemicals Legislation, Council
Regulation 793/93/EEC. RAR and Opinion by the
CSTEE available.
167
di-n-octyl phthalate (DOP) Under risk assessment in chemical legislation
Council Regulation 793/93/EEC.Not found in the
study
di-iso-nonyl phthalate (DINP) EFSA Scientific opinion. Evaluated under the
Existing Chemicals Legislation, Council Regulation
793/93/EEC. RAR available
26
di-iso-decyl phthalate (DIDP) EFSA Scientific opinion. Evaluated under the
Existing Chemicals Legislation, Council Regulation
793/93/EEC, RAR and Opinion by the CSTEE
available
37
* Risk Assessment of DEP, December 2005 by Norwegian Scientific Committee for Food Safety enclosed.
The Greenpeace investigation raises a general health and environmental concern about chemicals in perfumes, points out limits in the existing legislation against e.g. endocrine disruptors and states that, “traditional narrow risk assessment techniques are unlikely to provide adequate protection”.
It should be noted that the measurements carried out by Greenpeace were carried out on products prior to the effective date of the ban of certain phthalates in cosmetics and may thus necessarily not reflect current levels.
1.2 Traces and impurities COLIPA request
The Cosmetic Directive (76/768/EC) provides:
In article 4 paragraph 2 it is said for traces “The presence of traces of the substances listed in Annex II shall be allowed provided that such presence is technically unavoidable in good manufacturing practice and that it conforms with Article 2” (~ must not cause damage to human health).
And in article 6.1(g), it is stated that “impurities in the raw materials used” should not be regarded as ingredients.
According to COLIPA, traces of phthalates may leach unintentionally into cosmetic products through contact of the finished products or raw materials with plastic material (containers, pipes, pumps) during production or storage. In this context COLIPA (The European Cosmetic Toiletry and Perfumery Association) has asked the Commission to evaluate whether the presence of such trace levels would constitute a risk to consumers.
The problem about traces of phthalates in cosmetic products has been discussed at the cosmetic working group meetings and France has submitted a paper proposing a limit of 60 ppm of DEHP in cosmetic products.
1.3 Scientific data from the open literature submitted with the mandate
The study by Swan et al. “Decrease in anogenital distance among male infants with prenatal phthalate exposure” published May 2005, as well as scientific comments from COLIPA on this study has been received by the European Commission.
A second study by Duty et al. “Personal Care Product Use predicts Urinary Concentrations of some Phthalate Monoesters” published November 2005 has also been received.
A third study by Main et al. “Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Three Months Old Infants” published in September 2005 has also been received.
2.TERMS OF REFERENCE
1. Does the SCCP see any need to update its opinion on the safe use of diethyl phthalate
(DEP) in cosmetics with the new scientific data provided?
If so, do the data provided by Greenpeace allow an assessment of the level of risk from current use and the determination of a safe consumer exposure from the scientific data provided?
2. Do the data provided by Greenpeace, the literature and where available,
CSTEE/SCHER and EFSA indicate a risk for the consumers from the presence of the following phthalates, (which have so far not been evaluated or regulated under the cosmetics directive), when present at the levels found by Greenpeace in cosmetic products: DMP, DIBP, DCHP, DINP and DIDP?
If so, do the data allow an assessment of the level of risk from current levels and the determination of a safe consumer exposure?
3. Do the data provided support the safety of traces of up to 100 ppm total or per
substance in cosmetics products of those phthalates (DEHP, DBP and BBP), which are banned in cosmetics products?
3.OPINION
Question 1Does the SCCP see any need to update its opinion on the safe use of
diethyl phthalate (DEP) in cosmetics with the new scientific data provided?
If so, do the data provided by Greenpeace allow an assessment of the level
of risk from current use and the determination of a safe consumer
exposure from the scientific data provided?
In the TNO report (2005) that formed the basis of the Greenpeace report, the range of diethyl phthalate (DEP) in perfume was from 0.4 to 22299 mg/kg or 2.23% with a median concentration of 1073 mg/kg. These concentrations are within the range allowed for DEP use in perfumes.
The SCCP does not see any need to update its previous opinions (SCCNFP/411/01 adopted during the 20th plenary meeting of 4 June 2002 and reiterated in opinion n° SCCNFP/0767/03, adopted during the 26th plenary meeting of 9 December 2003). DEP may be used as fragrance solvent at a maximum concentration of 50% (hypothetical usage volume of 1 ml). This results in a potential exposure of 28 mg/d giving a Margin of Safety (MoS) of 321 or as an ethanol denaturant at a maximum concentration of 1% (hypothetical usage volume of 10 ml), from which it results a 5.6 mg/d potential exposure giving a MoS of 1607. The worst case MOS calculation made by SCCNFP for all cosmetics was 161, assuming 10% of diethyl phthalate in all cosmetic products.
This view was supported by the Panel on Food Additives, Flavourings, Processing Aids, Materials in Contact with Food and Cosmetics of the Norwegian Scientific Committee for Food Safety (05/406-8 final, 2005). They were of the opinion that new studies on DEP published later than 2003 and reviewed in their assessment, did not provide sufficient new information to change the conclusions given in the safety assessments of the use of DEP in cosmetics adopted by SCCNFP.
Question 2Do the data provided by Greenpeace, the literature and where available, CSTEE/SCHER and EFSA indicate a risk for the consumers from the
presence of the following phthalates, (which have so far not been
evaluated or regulated under the cosmetics directive), when present at the
levels found by Greenpeace in cosmetic products: DMP, DIBP, DCHP, DINP
and DIDP?
Di-methyl phthalate (DMP),Di-isobutyl phthalate (DIBP), Di-cyclohexyl phthalate (DCHP)
There is little data up to modern standards on the phthalates listed in the table below. The only data available was from the respective IUCLID Chemical Data Sheets and EFSA (2004). EFSA categorised DMP and DCHP as List 7 ‘Substances for which some toxicological data exist, but for which an Acceptable Daily Intake (ADI) or a Tolerable Daily Intake (TDI) could not be established. Required additional information should be furnished.’ No dermal absorption data was found. DIBP was categorised as List 8 ‘Substances for which no or only scanty and inadequate data were available’.
Name EINECS / CAS Maximum perfume concentration (mg/kg) NOAEL mg/kg/day
Critical effect
Di-methyl phthalate (DMP) 205-011-6 / 131-11-3 2982 600
Maternal toxicity
Di-isobutyl phthalate (DIBP) 201-553-2 / 84-69-5 38 50
effects on liver
Di-cyclohexyl phthalate (DCHP) 201-545-9 / 84-61-7
3 -
DMP was found at a concentration as high as 2982 mg/kg or 0.3% in one perfume, in the other 15 perfumes the concentration was between 0.1 and 1.9 mg/kg.
COLIPA has stated (letter of 29 November 2002) that “there is no intentional use of DMP…as a cosmetic ingredient’. Consequently, the presence and purpose of dimethyl phthalate at the maximum concentration found is unclear.
The NOAEL for maternal toxicity was 600 mg/kg bw/day DMP. In contrast to the observed maternal toxicity, there was no effect of DMP treatment on any parameter of embryo/foetal development (IUCLID, 2000).
Dermal absorption of DMP was not reported but described as less than that of DEP (5%). (Elsisi et al, 1989)
DMP and its metabolite monomethyl phthalate (MMP) have been investigated in several studies. In rats, exposure to DMP did not alter sexual differentiation of the male rat. Initially it seemed that in man, there was a possible association of abnormal sperm morphology in the presence of MMP. Interestingly, Hauser et al (2006) found no dose response link with sperm concentration, motility or morphology due to MMP, monoethyl phthalate and the DEHP metabolites. (Duty et al, 2003; Gray et al, 2000; Hauser et al, 2006)
Margin of Safety (MoS) Calculation for Traces of DMP in cosmetics
A Margin of Safety, using the highest concentration (2982 mg/kg or 0.3%) found, can be calculated, based on NOAEL and dermal absorption less than 5% reported as a percentage in the literature (Elsisi et al, 1989).
Only dermal exposure will be considered in the safety calculation.
Maximum dermal absorption: < 5% Exposure to all cosmetic products: 17.79 g/d Default human body weight: 60 kg
Systemic Exposure Dose (SED) 17.79 x 1000 x 0.3% x 5% / 60 = 0.0445 mg/kg
No observed adverse effect level (NOAEL) = 600 mg/kg bw/day (maternal toxicity in rats)
DMP Margin of Safety NOAEL / SED = 13500
Conclusion
DMP was found at concentration of 2982 mg/kg or 0.3% in one perfume, in the other 15 perfumes the concentration was between 0.1 and 1.9 mg/kg. Using a worst case scenario, the Margin of Safety was found to be high. This suggests that unintentional exposure from perfume and other cosmetics at the levels found in this study would have no measurable risk for the consumer.
DCHP was found in only 1/36 perfume samples at a concentration of 3 mg/kg.
There appears to be no recent work on DCHP. The 90-day studies reported in the IUCLID data sheet (IUCLID, 2000) do not seem to be according to modern standards. No NOAEL was derived from these studies. EFSA (2004) requested additional data: reproduction and teratogenicity studies, test for gene mutation and in vitro mammalian cell chromosome aberration tests.
Conclusion
Despite the lack of adequate toxicological data, the low concentration (3 mg/kg) of DCHP found in only one sample of perfume, suggest unintentional exposure from perfume and other cosmetics would have no measurable risk for the consumer.
DIBP was found in 20/36 perfumes with concentrations ranging from 0.2 - 38 mg/kg. It is considered a possible substitute for DBP. The NOAEL for oral toxicity was 50 mg/kg DIBP, based on liver effects. There was no data on skin absorption. (IUCLID, 2000)
If dosed at 600 mg/kg bw/day to pregnant rats on gestation days 7 –21, male offspring showed similar testicular and developmental effects as found with DBP and DEHP. Further developmental and postnatal studies are needed to identify the reproductive effects of DIBP. (Borch, 2006)
DIBP is classified by ECB as toxic to reproduction category 2, R61 (may cause harm to the unborn child) and category 3, R62 (possible risk of impaired fertility). It is therefore prohibited from use in cosmetic products.
Conclusion
The low concentrations of DIBP (0.2 - 38 mg/kg) found in samples of perfume suggest unintentional exposure from perfume and other cosmetics would pose no measurable risk for the consumer.
Di-iso-nonyl phthalate (DINP) and di-iso-decyl phthalate (DIDP)
Name EINECS / CAS Highest
perfume
concentration in
mg/kg
NOAEL mg/kg/day Status
di-iso-nonyl phthalate (DINP) 271-090-9 & 249-079-5 / 68515-48-0 & 28553-12-0 26 15 (rat) Increased liver and kidney weight
5% response BMD of 12*
15 -1000
increased liver and kidney weight, testes
RAR Conclusion (ii)** EFSA (2005a)
CSTEE (2001a)
Evaluated under the Existing Chemicals Legislation, Council
Regulation 793/93/EEC. RAR available di-iso-decyl phthalate (DIDP)
271-090-4 & 247-977-1/
68515-49-1 & 26761-40-0
37 15
13-week oral study in dogs 25
50 –600
increased liver and thyroid weight
RAR Conclusion (iii) and (ii)**
EFSA (2005b)
CSTEE (2001b)
Evaluated under the Existing Chemicals Legislation, Council
Regulation 793/93/EEC, RAR available
* BMD benchmark dose
** RAR Conclusion (ii) There is at present no need for further information and/or testing and for risk reduction measures beyond those which are being applied already
Conclusion (iii) There is a need for limiting the risks; risk reduction measures which are already being applied shall be taken into account
DINP
DINP was found in only 1/36 perfume samples at a concentration of 26 mg/kg.
The toxicological effects for DINP were an increased incidence of spongiosis hepatis, accompanied by increased serum levels of liver enzymes in males and increases in absolute and relative liver and kidney weights in both sexes. EFSA (2005a) used a NOAEL of 15 mg/kg bw/day for non-peroxisomal proliferation-related chronic hepatic and renal effects derived from a combined chronic/carcinogenicity study in rats. From the same data, CSTEE (2001) calculated a 5% response benchmark dose of 12 mg/kg/d using spongiosis hepatis as the critical endpoint of the risk characterization. This will not alter the Margin of Safety from perfume use.
EFSA derived a TDI for DINP of 0.15 mg/kg bw, using the NOAEL of 15 mg/kg bw/day and an uncertainty factor of 100.
Margin of Safety (MoS) Calculation for Traces of DINP in cosmetics
A Margin of Safety can be calculated, using the highest concentration (0.003%) found, based on NOAELs and dermal absorption of 4 % for DINP reported as a percentage in the literature (Elsisi et al, 1989).
Only dermal exposure will be considered in the safety calculation.
Exposure to all cosmetic products: 17.79 g/d
Default human body weight: 60 kg
Maximum dermal absorption: 4 %
Systemic Exposure Dose (SED) 17.79 x 1000 x 0.003% x 4% / 60 = 0.00036 mg/kg/d No observed adverse effect level (NOAEL) = 15 mg/kg bw/d (oral toxicity in liver in rats)
DINP Margin of Safety NOAEL / SED = 41666
Systemic exposure of DINP from cosmetics is 0.24% of the TDI for DINP of 0.15 mg/kg/d derived by EFSA, (2005a)
Exposure to DINP from cosmetics is extremely low compared with exposure from other sources, such as food and non-food products (EFSA, 2005a; CSTEE, 2004, RAR, 2003). Thus the inadvertent occurrence of DINP in cosmetics does not seem to be a concern for consumer health.
DIDP
DIDP was found in 5/36 perfume samples at concentrations ranging from 1.5 - 37 mg/kg. The EFSA Panel concluded that a NOAEL of 15 mg/kg bw/day for DIDP from a 13-week oral study in dogs (a non-sensitive species to peroxisome proliferation) should be used in the risk assessment and in a 2-year rat study where there was a decrease of F2 offspring survival with a NOAEL of 33 mg/kg bw/day. From the same data, CSTEE (2001b) calculated a NOAEL of 25 mg/kg/d based on the lowest observed adverse effect level (LOAEL). Liver changes were seen at higher dose levels with a lowest observed adverse effect level LOAEL of 77 mg/kg bw/day and 88 mg/kg bw/day for male and female dogs respectively. Using the NOAEL of 15 mg/kg bw/day and of an uncertainty factor of 100, a TDI for DIDP of 0.15 mg/kg bw was derived (EFSA 2005b).
Margin of Safety (MoS) Calculation for Traces of DIDP in cosmetics
A Margin of Safety can be calculated, using the highest concentration (0.0037 %) based on NOAELs and dermal absorption of <1 % for DIDP reported as a percentage in the literature (Elsisi et al, 1989) though due to low recovery this may be underestimated. Only dermal exposure will be considered in the safety calculation.
Exposure to all cosmetic products: 17.79 g/d Default human body weight: 60 kg Maximum dermal absorption: 1 % DIDP
Systemic Exposure Dose (SED) 17.79 x 1000 x 0.0037% x 1% / 60 = 0.000009 mg/kg/d
No observed adverse effect level (NOAEL) = 15 mg/kg bw/d (oral toxicity in liver in dogs)
DIDP Margin of Safety NOAEL / SED = 1666666
Systemic exposure from cosmetics is 0.006% of the TDI of 0.15 mg/kg/d defined by EFSA (2005b). Exposure to DIDP from cosmetics is extremely low compared with exposure from other sources, such as food and non-food products (EFSA, 2005b; CSTEE, 2004, DIDP RAR, 2003). Thus the inadvertent occurrence of DIDP in cosmetics does not seem to be a concern for consumer health.
It was also noted that in 5/36 perfumes, DIDP and DINP were found below ‘reporting limit’. Although not specified, this suggests a mixture of DINP/DIDP. The EFSA AFC Panel noted also that DIDP and DINP (phthalic acid, diester with primary saturated C8-C10 branched alcohols, C9 rich, CAS n° 28553-12-0 and 68515-48-0, PM/REF 75100) are mixtures that overlap chemically with each other and cannot analytically be distinguished clearly if present in a mixture. For this reason, a group restriction for migration from food contact materials for DINP and DIDP was considered and rejected, as though both primarily affect the liver but the end-points indicate that different mechanisms are involved (EFSA, 2005c).
Question 3: Do the data provided support the safety of traces of up to 100 ppm total or
per substance in cosmetics products of those phthalates (DEHP, DBP and BBP), which are banned in cosmetics products?
Name EINECS / CAS Highest
concentration
in mg/kg
NOAEL mg/kg bw/day Critical effect Status
di-(2-ethylhexyl) phthalate (DEHP) 204-211-0/
117-81-7
167 4.8 testicular and developmental toxicity
88-1000
increased liver and kidney weight, testes
RAR Conclusion (ii ) and (iii)*
CSTEE (2004b) EFSA (2005d)
Evaluated under the Existing Chemicals Legislation, Council
Regulation 793/93/EEC. RAR
Annex 1 607-317-00-9 Repr. Cat. 2; R60-61 (fertility;development)
Name EINECS / CAS Highest
concentration
in mg/kg
NOAEL mg/kg bw/day
Critical effect Status
di-n-butyl phthalate (DBP) 201-557-4/ 84-74-2.
14 NOAEL 50
reproductive effects
LOAEL 2
NOAEL 62.5 -152
increased peroxisomal proliferation
RAR Conclusion (ii)*
CSTEE (2001c)
EFSA (2005e)
Evaluated under the Existing Chemicals Legislation, Council
Regulation 793/93/EEC, RAR
Annex 1 607-318-00-4 Repr. Cat. 2; R61
(development), Repr. Cat. 3; R62 (fertility) - N; R50 Benzylbutyl
phthalate (BBP) 201-622-7 / 85-68-7
110 NOAEL 50
reproductive effects
NOAEL 50
reproductive effects
RAR Draft Conclusion (ii)*
SCHER (2005) EFSA (2005f)
Annex 1 607-430-00-3 Repr. Cat. 2; R61
(development), Repr. Cat. 3; R62 (fertility) - N; R50-53
* RAR Conclusion (ii): There is at present no need for further information and/or testing
and for risk reduction measures beyond those which are being applied already.
Conclusion (iii): There is a need for limiting the risks; risk reduction measures which are already being applied shall be taken into account.
The main concerns relating to these substances are the reproductive effects. In adult rats, the testis is the target. DBP and DEHP have effects on germ cell development/depletion, BBP affects epididymal spermatozoa concentration. Anti-androgenic effects have also been noted in foetal rats. The human epidemiological evidence is equivocal. In rats, the phthalate syndrome of effects on reproductive development has parallels with the reported human testicular dysgenesis syndrome, although no cause/effect relationship has been established after exposure of humans to phthalate esters.
Swan et al. (2005) suggested in humans that there was a relationship between the concentration of phthalate metabolites in maternal prenatal urine and the anogenital distance (AGD) and anogenital index (AGI: AGD/weight) in male offspring similar to that found in rats. The maternal urinary phthalate levels were very low (ng/ml) compared with the rat studies (effects at ≥100mg//kg bw/day). However, since all boys were considered normal (no malformation) and with no historical data on AGD in boys, extrapolation to solely phthalate effects is difficult.
More recent studies examining the wider concept of testicular dysgenesis syndrome (TDS) and phthalate effects are equivocal. The TDS hypothesis argues that any factor that causes mal-development is likely to result in TDS disorders, and this includes well-established genetic disorders (Skakkebaek et al. 2001); it is also likely to be affected by maternal lifestyle (Scott et al, 2007). Thus phthalates may be a contributory factor in a complex chain of TDS, but not the only cause of TDS.
The target organ for oral sub-acute and sub-chronic toxicity in rats for these phthalates was the liver (increased liver weights and significant changes in liver peroxisome enzyme activities) that are generally considered to be species-specific. Human liver appears to show slight or no response to peroxisome proliferation, possibly explained by a low level of PPAR α found in human livers (1-10% of the level found in rat and mouse liver).
Diethylhexyl Phthalate (DEHP) was found in 14/36 perfume samples at concentrations
ranging from 1 - 167 mg/kg.
Margin of Safety (MoS) Calculation of DEHP in cosmetics
A Margin of Safety can be calculated, using the highest concentration (0.0167 %), based on
NOAEL and worst-case estimate of 5 % dermal absorption for DEHP reported in the literature (EU Risk Assessment DEHP, 2003). There are no adequate human studies, but rat
skin has dermal absorption of 20% DEHP and has been shown to be 4-times more permeable than human skin. This would seem to be an overestimate as Elsisi et al (1989) showed that less than 15% of the applied dose was absorbed through rat skin.
Only dermal exposure will be considered in the safety calculation.
Exposure to all cosmetic products 17.79 g/d
Default human body weight: 60 kg
NOAEL: 4.8 mg/kg/d based on testicular effects in a three generation guideline study (Wolfe et al, 2003, cited in DEHP RAR, 2003). The NOAEL has been confirmed in
the opinions of the CSTEE 2004b and EFSA 2005d.
Maximum dermal absorption 5 % estimated worst-case
MoS for maximum traces of DEHP found in one perfume (167 ppm)
Systemic Exposure Dose (SED) = 17.79 x 1000 x 0.0167% x 5% / 60 = 0.00247 mg/kg/d MoS (NOAEL / SED) = 4.8 / 0.00247 = 1920
Based on the highest level found in one perfume, the systemic exposure from cosmetics would be 5% of the TDI of 0.05 mg/kg/d derived by EFSA, (EFSA 2005d; EU Risk Assessment DEHP, 2003; CSTEE, DEHP, 2004b).
In light of the MoS based on 167ppm DEHP, the Member State proposal of a 60 ppm DEHP limit in cosmetic products may not be required.
Exposure to DEHP from cosmetics is low compared with exposure from other sources, such as food and non-food products. Thus the inadvertent occurrence of DEHP at trace levels in cosmetics does not seem to be a concern for consumer health.
Dibutyl Phthalate (DBP) was found in 20/36 perfume samples at concentrations ranging from 0.1 – 14 mg/kg.
Margin of Safety (MoS) Calculation for Traces of DBP in cosmetics
A Margin of Safety was calculated based on the LOAEL as no NOAEL could be established and on dermal absorption of 5 % for DBP as reported in the literature (Bronaugh et al. 1982, Elsisi et al. 1989 cited in RAR and an in vitro study (Scott et al. cited in RAR).
Only dermal exposure will be considered in the safety calculation.
LOAEL: A developmental toxicity study in the rat (Lee et al., 2004 cited by EFSA 2005e) with dietary exposure to DBP from gestation day 15 to the end of lactation
(postnatal day 21), showed effects on the development of male and female
offspring at lower doses than found previously. A NOAEL could not be established.
A LOAEL of 2 mg/kg bw/d feed was derived, since the effects were reversible at all
dose levels, particularly the lowest dose level (20 mg/kg feed, equivalent to 1.5 to
3 mg/kg bw/day) combined with other reproductive toxicity studies, with longer
exposure periods, approximately 30-fold higher NOAELs or LOAELs were
determined (RAR).
Exposure to all cosmetic products: 17.79 g/d
Default human body weight: 60 kg
MoS at highest concentration, 14ppm, found in perfume
SED with 14 ppm (.0014%) = 17.79 x 1000 x 0.0014% x 5% / 60 = 0.0002 mg/kg/d DBP = LOAEL / SED = 2 / 0.0002 = 10000
MoS if technically unavoidable traces up to 100 ppm DEHP found in all cosmetic products
Systemic Exposure Dose (SED) = 17.79 x 1000 x 0.01% x 5% / 60 = 0.00148 mg/kg/d DBP MoS (traces 100ppm) = LOAEL / SED = 2 / 0.00148 = 1350
If systemic exposure of DBP from cosmetics was up to 100 ppm, this would be 15% of the TDI for DBP of 0.01 mg/kg bw/day defined by EFSA who used an uncertainty factor of 200 (EFSA, 2005e; EU Risk Assessment DBP, 2003; CSTEE, DBP, 2001c).
Exposure to DBP from cosmetics is extremely low compared with exposure from other sources, such as food and non-food products (EFSA, 2005e; CSTEE 2004, RAR 2003). Thus the inadvertent occurrence of DINP in cosmetics at trace levels does not seem to be a concern for consumer health.
Benzyl Butyl Phthalate (BBP) was found in 9/36 perfume samples at concentrations ranging from 0.1 – 110 mg/kg
Margin of Safety (MoS) Calculation for Traces of BBP in cosmetics
A Margin of Safety can be calculated, based on NOAELs and dermal absorption 5 % based on the available data, dermal absorption is considered to be 5% as a worst case estimate (RAR)
Only dermal exposure will be considered in the safety calculation.
Assuming a worst case of 110ppm (0.011%) BBP in all cosmetic products
NOAEL: 50 mg/kg/d (Tyl et al. 2004, cited in RAR) based on a two generation study in SD rats
Exposure to all cosmetic products: 17.79 g/d
Default human body weight: 60 kg
Systemic Exposure Dose (SED) = 17.79 x 1000 x 0.011% x 5% / 60 = 0.00163 mg/kg/d BBP MoS = NOAEL / SED = 50 / 0.00163 = 31250
Systemic exposure of BBP from cosmetics is 3.26% of the 0.5 mg/kg/d TDI defined by EFSA (2005f).
SCHER (2005) characterized the risk for consumers by using the NOAEL for developmental toxicity as a starting point and found the MoS-values derived are >> 1000. (EFSA 2005f; EU Risk Assessment BBP, 2004; SCHER, BBP, 2005)
Exposure to BBP from cosmetics is extremely low compared with exposure from other sources, such as food and non-food products (EFSA 2005f; CSTEE 2004, RAR 2003). Thus the inadvertent occurrence of BBP in cosmetics at trace levels does not seem to be a concern for consumer health.
3.3. Possible source of phthalates occurring in perfumes Two perfumes that had low concentrations of DEP (37 and 27 mg/kg) and also measurable levels of DIBP (5.5 and 1.9 mg/kg), DBP (2.9 and 1.8 mg/kg) and DEHP (25 and 0 mg/kg) were used to check the hypothesis that the DEP could have leached from the polymers of the container. The results showed that the ratio of all the four phthalates was similar between the perfumes, the leaching fluid and the polymer tubing, but the levels in the perfume were 100 fold higher. The study authors suggested that the migration of the phthalates was from the perfume into the tubing of the final packaging.
There was no consideration that the phthalates found in the 2 perfumes could have leached unintentionally through contact of the raw materials with plastic material (containers, pipes, pumps) during an earlier stage of production.
Ref.: TNO, 2005
3.4. Discussion The Cosmetic Directive (76/768/EC) states in article 4 paragraph 2: “The presence of traces of the substances listed in Annex II shall be allowed provided that such presence is technically unavoidable in good manufacturing practice and that it conforms with Article 2” and in article 6.1(g), it is stated that “impurities in the raw materials used ” should not be regarded as ingredients.
COLIPA has pointed out that traces of phthalates may leach into cosmetic products. DMP, DBP, BBP and DEHP are not cosmetic ingredients. DBP, BBP and DEHP are used extensively as plastic softeners and may be found in cosmetics as leachates from contact with plastic materials either during the processing of the raw materials or from the packaging of the finished product.
Thirty-six perfumes were analysed for ten phthalates. One perfume sample was free of any phthalates and one phthalate, di-n-octyl phthalate was not found in any of the perfume samples.
Range and ranking of phthalates found in the perfumes (taken from TNO, 2005).
Name N/36 Range mg/kg Reporting limit
mg/kg
di-n-octyl phthalate (DOP) 0 0 0.1 di-cyclohexyl phthalate (DCHP)
1 3 0.1 di-n-butyl phthalate (DBP) 21 0.1 - 14 0.1 di-iso-nonyl phthalate (DINP)
1 (5*) 26 1 di-iso-decyl phthalate (DIDP)
5 (5*) 1.5 - 37 1 di-isobutyl phthalate (DIBP) 20 0.2 - 38 0.1 benzylbutyl phthalate (BBP) 9 0.1 - 110 0.1 di-(2-ethylhexyl) phthalate (DEHP)
14 1 - 167 1 di-methyl phthalate (DMP) 16 0.1 - 2982 0.1 di-ethyl phthalate (DEP) 34 0.4 - 22299 1 * found below reporting limit, not specified but suggesting a mixture of DINP/DIDP
Seven phthalates were found at low concentrations and were not found in all perfume samples. Ranked from lowest to highest maximum concentration (3 - 167mg/kg), DCHP,
DBP, DINP, DIDP, DIBP, BBP, DEHP. This suggests that they were present as traces and/or impurities, not used intentionally in the perfumes.
DMP and DEP were found at higher concentrations, 0.3% and 2.23% respectively in the perfumes. DEP is permitted in perfume and has low toxicity. DMP is not used in cosmetics according to COLIPA. Toxicity data for DMP is sparse and not to modern standards. The Margin of Safety for DMP was large. There is some equivocal epidemiological evidence for both DMP and DEP of impairment of some reproductive function markers (sperm motility, concentration, morphology, DNA damage) in the human male, but the results are not consistent. Neither appears to be linked with perinatal alteration of sexual differentiation in rats.
Greenpeace raised a general health and environmental concern about chemicals in perfume. It should be noted that the studies carried out on products prior to the effective date of the ban of certain phthalates in cosmetics and thus may not reflect current levels. Greenpeace points out limits in the existing legislation against e.g. endocrine disruptors and states that, “traditional narrow risk assessment techniques are unlikely to provide adequate protection”. In the case of the phthalates described in this document, the calculated Margins of Safety for the phthalates where there is adequate toxicological data suggest that there are very wide margins of safety. It must also be stressed in calculating the MoS, the worst-case scenario was used: the SCCNFP-value of 17.79 g/day exposure, with total skin surface coverage >15000cm2, for the consumer using a set of cosmetic products containing the same ingredient. RIVM (2005) estimated that the skin surface exposed would be only 100 cm2 for perfume and200 cm2 for eau de toilette.
The toxicity of those phthalates, where data is sparse, is low. The toxicological effects appear to target liver or testis but the effects are less than for other phthalates.
The levels of phthalates found in perfumes, either as impurities, technically unavoidable during manufacturing or as a fragrance ingredient would be a minor contribution to the global exposure from other sources.
Exposure via inhalation of phthalate impurities (< 100 ppm in cosmetic products) from spray cosmetic products is considered to be insignificant and has not been taken into account in the safety evaluation
4.CONCLUSION
Question 1: Does the SCCP see any need to update its opinion on the safe use of diethyl phthalate (DEP) in cosmetics with the new scientific data provided?
In response to the question 1, the SCCP is of the opinion that there is no need to update its opinion on the safe use of diethyl phthalate (DEP) (doc. n° SCCNFP/0441/01) in cosmetics on the basis of the new scientific data provided
Question 2: Do the data provided by Greenpeace, the literature and where available, CSTEE/SCHER and EFSA indicate a risk for the consumers from the presence
of the following phthalates, (which have so far not been evaluated or
regulated under the cosmetics directive), when present at the levels found by
Greenpeace in cosmetic products: DMP, DIBP, DCHP, DINP and DIDP?
If so, do the data allow an assessment of the level of risk from current levels
and the determination of a safe consumer exposure?
Despite there being a lack of adequate toxicological data for some of this group of phthalates, and in view of the low concentrations found in the samples of perfume analysed, there would be no quantifiable risk for the consumer.
Question 3: Do the data provided support the safety of traces of up to 100 ppm total or per substance in cosmetics products of those phthalates (DEHP, DBP and
BBP), which are banned in cosmetics products?
In view of the high Margin of Safety (MoS) determined for these three phthalates, the SCCP is of the opinion that traces of up to 100 ppm total or per substance do not indicate a risk to the health of the consumer.
5.MINORITY OPINION
Not applicable
6.REFERENCES
References with mandate
CICADS 52 on Diethyl phthalate
COLIPA submission I on traces of phthalate esters DBP, DEHP and BBP on cosmetic products CSTEE, (2001b), Scientific opinion on the results of the Risk Assessment of 1,2-benzenedicarboxylic acid di-C9-C11-branched alkyl esters, C10-rich and di-
“isodecyl”phthalate (DIDP) (June 2001)
CSTEE, (2001c), Scientific opinion on the results of the Risk Assessment of Dibutylphthalate (DBP) (April 2001)
CSTEE, (2004b) Opinion on the results of a second risk assessment of: bis(2-ethylhexyl) phthalate (DEHP) human health part. Csteeop/DEHP/080104 D(04)
Duty et al. “Personal Care Product Use predicts Urinary Concentrations of some Phthalate Monoesters”
EFSA (2005a), Scientific opinion on DINP (July 2005)
EFSA (2005b), Scientific opinion on DIDP (July 2005)
EFSA (2005d), Scientific opinion on bis-(2-ethylhexyl)-phthalate (DEHP) (June 2005)
EFSA (2005e), Scientific opinion on DBP (June 2005)
EFSA (2005f), Scientific opinion on BBP (June 2005)
France document: ?Seuil acceptable pour des traces de DEHP dans les produits cosmetiques?
Greenpeace International Report 2005. Perfume, an Investigation of Chemicals in Perfumes Main KM, Mortensen GK, Kaleva MM, Boisen KA, Damgaard IN, Chellakooty M, Schmidt IM, Suomi AM, Virtanen HE, Petersen DV, Andersson AM, Toppari J, Skakkebaek NE.
(2006). Human Breast Milk Contamination with Phthalates and Alterations of
Endogenous Reproductive Hormones in Three Months Old Infants. Environmental
Health Perspectives.114(2):270-6.
Nohynek,G.J. Anogenital Distance in Male Infants and Correlation with Maternal Exposure to Phthalates during Pregnancy: Is there a Health Risk?
Norwegian Scientific Committee for Food Safety: Risk Assessment of Diethyl phthalate (DEP) on cosmetics. December 2005
Risk Assessment Report under Council Regulation 793/93/EEC on DINP (2003)
Risk Assessment Report under Council Regulation 793/93/EEC on DIDP (2003)
Risk Assessment Report under Council Regulation 793/93/EEC on DBP (2003)
Risk Assessment Report under Council Regulation 793/93/EC on DEHP (2003)
Risk Assessment Human Health on (BBP) (March 2004)
SCHER (2005), Scientific opinion on “Risk Assessment Report on Benzyl Butyl Phthalate (BBP) Human Health Part”
Swan SH, Main KM, Liu F, Stewart SL, Kruse RL, Calafat AM, Mao CS, Redmon JB, Ternand CL, Sullivan S, Teague JL; Study for Future Families Research Team. (2005). Decrease in Anogenital Distance among Male Infants with prenatal Phthalate Exposure. Envir.
Health Persp. 113(8):1056-61
TNO-report R&I-A R 2005/011 Phthalates and Artificial Musks in Perfumes
Other references
Borch, J, Marta Axelstad, Anne Marie Vinggaard, Majken Dalgaard (2006). Diisobutyl phthalate has comparable anti-androgenic effects to di-n-butyl phthalate in fetal rat testis. Toxicology Letters 163:183-90
Bronaugh RL, Stewart RF, Congdon ER (1982). Methods for in vitro percutaneous absorption studies. II. Animal models for human skin. Toxicol Appl Pharmacol. 62:481-8. CSTEE, (2001a), Opinon on the results of the Risk Assessment of: 1,2-Benzenedicarboxylic acid, di-C8-10-branched alkyl esters, C9-rich and di-"isononyl" phthalate (Human
Health Effects) (October 2001)
CSTEE, (2004a) Opinion on "Assessment of the bioavailability of certain elements in toys".
(June 2004)
Duty SM, Silva MJ, Barr DB, Brock JW, Ryan L, Chen Z, Herrick RF, Christiani DC, Hauser R (2003). Phthalate exposure and human semen parameters. Epidemiology 14:269-277 EFSA (2004), Statement of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food (AFC Panel) on the re-classification of some phthalates for consistency with the new SCF guidelines for food contact materials (May 2004).
EFSA (2005c), Statement of the Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission on the possibility of allocating a group-TDI for Butylbenzylphthalate (BBP), di-Butylphthalate (DBP), Bis(2-ethylhexyl) phthalate (DEHP), di- Isononylphthalate (DINP) and di-Isodecylphthalate (DIDP)
Elsisi A.E., Carter D.E. and Sipes I.G. (1989). Dermal absorption of phthalate diesters in rats. Fund Appl Tox 12, 70-77
Gray LE Jr, Ostby J, Furr J, Price M, Veeramachaneni DN, Parks L (2000). Perinatal exposure to the phthalates DEHP, BBP, and DINP, nut not DEP, DMP, or DOTP, alters sexual differentiation of the male rat. Toxicol Sci. 58:350-65
Hauser R, Meeker JD, Duty S, Silva MJ, Calafat AM. (2006). Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites.
Epidemiology, 17:682-91
IUCLID data sheets available at http://ecb.jrc.it/esis/
RIVM Report 320104 001/2005 Bremmer H.J., Prud'Homme de Lodder L.C.H., van Engelen J.G.M. (2005) Cosmetics Fact Sheet to assess the risks for the consumer, Updated version for ConsExpo4
Scott HM, Hutchison GR, Mahood IK, Hallmark N, Welsh M, De Gendt K, Verhoeven G, O’Shaughnessy P, Sharpe RM (2007). Role of androgens in fetal testis development and dysgenesis Endocrinology. February 8, 2007 as doi:10.1210/en.2006-1622 Skakkebaek NE, Rajpert-De Meyts E, Main KM (2001). Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects. Hum
Reprod 16:972-978
英语介词用法口诀 早、午、晚要用in，at黎明、午夜、点与分。 年、月、年月、季节、周，阳光、灯、影、衣、冒in。 将来时态in...以后，小处at大处in。 有形with无形by，语言、单位、材料in。 特征、方面与方式，心情成语惯用in。 介词at和to表方向，攻击、位置、恶、善分。 日子、日期、年月日，星期加上早、午、晚， 收音、农场、值日on，关于、基础、靠、著论。 着、罢、出售、偷、公、假，故意、支付、相反，准。 特定时日和"一……就"，on后常接动名词。 年、月、日加早、午、晚，of之前on代in。 步行、驴、马、玩笑on，cab，carriage则用in。 at山脚、门口、在当前，速、温、日落、价、核心。 工具、和、同随with，具有、独立、就、原因。 就……来说宾译主，对、有、方状、表细分。 海、陆、空、车、偶、被by，单数、人类know to man。 this、that、tomorrow，yesterday，next、last、one。 接年、月、季、星期、周，介词省略已习惯。 over、under正上下，above、below则不然， 若与数量词连用，混合使用亦无关。' beyond超出、无、不能，against靠着，对与反。 besides，except分内外，among之内along沿。 同类比较except，加for异类记心间。 原状because of,、owing to、due to表语形容词 under后接修、建中，of、from物、化分。 before、after表一点, ago、later表一段。 before能接完成时，ago过去极有限。 since以来during间，since时态多变换。 与之相比beside，除了last but one。 复不定for、找、价、原，对、给、段、去、为、作、赞。 快到、对、向towards，工、学、军、城、北、上、南。 but for否定用虚拟，复合介词待后言。 ing型由于鉴，除了除外与包合。 之后、关于、在......方面，有关介词须记全。 in内to外表位置，山、水、国界to在前。
英语介词用法大全 TTA standardization office【TTA 5AB- TTAK 08- TTA 2C】
介词（The Preposition）又叫做前置词，通常置于名词之前。它是一种虚词，不需要重读，在句中不单独作任何句子成分，只表示其后的名词或相当于名词的词语与其他句子成分的关系。中国学生在使用英语进行书面或口头表达时，往往会出现遗漏介词或误用介词的错误，因此各类考试语法的结构部分均有这方面的测试内容。 1. 介词的种类 英语中最常用的介词，按照不同的分类标准可分为以下几类： (1). 简单介词、复合介词和短语介词 ①.简单介词是指单一介词。如： at , in ,of ,by , about , for, from , except , since, near, with 等。②. 复合介词是指由两个简单介词组成的介词。如： Inside, outside , onto, into , throughout, without , as to as for , unpon, except for 等。 ③. 短语介词是指由短语构成的介词。如： In front of , by means o f, on behalf of, in spite of , by way of , in favor of , in regard to 等。 (2). 按词义分类 {1} 表地点（包括动向）的介词。如： About ,above, across, after, along , among, around , at, before, behind, below, beneath, beside, between , beyond ,by, down, from, in, into , near, off, on, over, through, throught, to, towards,, under, up, unpon, with, within , without 等。 {2} 表时间的介词。如： About, after, around , as , at, before , behind , between , by, during, for, from, in, into, of, on, over, past, since, through, throughout, till(until) , to, towards , within 等。 {3} 表除去的介词。如： beside , but, except等。 {4} 表比较的介词。如： As, like, above, over等。 {5} 表反对的介词。如： againt ,with 等。 {6} 表原因、目的的介词。如： for, with, from 等。 {7} 表结果的介词。如： to, with , without 等。 {8} 表手段、方式的介词。如： by, in ,with 等。 {9} 表所属的介词。如： of , with 等。 {10} 表条件的介词。如：
表示地点的介词 in、on、behind、next to、near、over、under (1) in在……里面：The pencil is in the desk. 铅笔在课桌里。 (2) on在……上面：There are some apple on the tree. 树上有些苹果。 (3) under在……下面/正下方：What's under your desk? 你书桌底下是什么？ (4) over在……正上方：There is a shelf over the table. 桌子上方有一个书架。 (5) above 在……斜上方：Raise your arms above your head. (6) below 在……斜下方：Her skirt came below her knees. (7) behind在……之后：There is a bike behind the tree. 树后有一辆自行车。 (8) next to在……旁边：There is a shop next to the school. 理发店隔壁是一家咖啡馆。 (9) near在……附近：My bed is near the window. 我的床在窗户旁。 (10) by在……旁：He was sitting by the window. (11) beside 在旁边He sits down beside Jim. 一组：over, above和on的用法 1) over指在…的正上方，表示垂直在上。如 There is a lamp over the desk. 2) above指在上方，属于斜上方。如： Raise your arms above your head. 3) on指在上面，表示两物体接触。如： There is a cup on the table. 二组：under / below的用法： 1) under在……下面/正下方： What's under your desk? 2) below 在……斜下方： Her skirt came below her knees 三组：in 和on表示“在……上” 1)门/窗一类——镶嵌在墙里的，用in; 2)字画一类——挂/贴在墙面上的，用on ( ) 1 He put up a map ___ the back wall because there was a hole ______ it. A. on; on B. at; in C. on; in D. on; at ( ) 2 There is a door___ the wall. A. on B. to C. of D.in 3)人/鸟其他东西在树上，用in; 4)枝叶果实长在树上的，用on ( ) 1 There are some birds singing___ the trees. A. in B. on C. at D. from ( ) 2 There are so many apples___ that tree. A.in B, on C of D.from
in on at 区别用法 妙计口诀 1.早、午、晚要用in， at黎明、午夜、点与分。 年、月、年月、季节、周， 阳光、灯、影、衣、帽用in。 将来时态in...以后， 小处at大处in。 有形with无形by， 语言、单位、材料in。 特征、方面与方式， 心情成语惯用in。 介词at和to表方向， 攻击、位置、恶、善分。 2.日子、日期、年月日，星期加上早、午、晚， 收音、农场、值日on，关于、基础、靠、著论。 着、罢、出售、偷、公、假，故意、支付、相反，准。 特定时日和“一……就”，on后常接动名词。 年、月、日加早、午、晚，of之前on代in。 步行、驴、马、玩笑on，cab，carriage则用in。 at山脚、门口、在当前，速、温、日落、价、核心。 如大体掌握上面介词用法口诀，就不易出错。下面对该口诀分别举例帮助你理解消化。 <1.>关于时间 早、午、晚要用in in the evening 在晚上 in the day 在白天 例： in the afternoon 在下午 in the morning 在早上 at黎明、午、夜、点与分 例 at dawn /at daybreak 在黎明时候 at night 在夜间 at noon 在中午 at midnight 在午夜 （以上短语都不用冠词）
at nine o'clock 在9点钟 at half past ten 在10点半 at ten thirty a.m. 在上午10点30分 at the weekend 在周末 at a quarter to two 1点45分 <2.>关于年、月、年月、季节、周 即在“来年”，在“某月”，在“某年某月” 但在某年某月某日则用on ，在四季，在第几周等都要用in。 in 1927 在1927年 in March 在三月 in December 1986 在1986年12月 in July l984 在1984年7月 in the first week of this semester这学期的第一周 in the third week 在第三周 in spring 在春季 <3.>关于日子、日期、年月日，星期加上早午晚 以下皆用on on October the first 1949 1949年10月1日 on May the first 5月1日 on the sixteenth 16号 on the second of January /on January the second 1月2日 on a summer evening 在夏天的一个夜晚 on New Year's Day 在元旦 on my birthday 在我的生日 on winter day 在冬天 on December 12th 1950 l950年12月12日 on Sunday 在星期天 on Tuesday morning 星期二早晨 但last night 昨夜；in the evening 在晚上 on time准时，in time及时，等则不同。 【注】in the Christmas holidays在圣诞节假期 in the eighteenth century 在十八世纪 in ancient times 在古代 in earlier times 在早期 in modern times 在现代，则用in，at the present time 现在，at the present day当今则用at。 <4.>关于年月日，加早午晚，of之前on代in on the morning of 18th 18日早晨 On the eve of their departure在临行前夕 <5.>阳光、灯、影、衣、冒 in
介词用法口诀： 早、牛、晚要用in at黎明、午夜、点与分 年、月、年月、季节、周，阳光、灯、影、衣、帽in 将来时态in表以后，小处at大处in 有形with无形by 语言、单位、材展in 早、午、晚要用in in the morning 在早上 in the afternoon 在下午 in the evening 在晚上 in the day在白天 at黎明、午、夜、点与分 at dawn, at daybreak^ 黎明时候 at noon在中午at night在夜间 at midnight 在午夜 at six o'clock 在6 点钟 at 7:30 （seven thirty）在7 点半 at the weeken血周末 年、月、年月、季节、周都用in in 1986 在1986 年 in March在三月 in July, 1983 1983 年7 月i n spring在春季 in the third week 在第三周 阳光、灯、影（树荫）、衣、冒（雨）in Don't read in dim light.切勿在暗淡的灯光下看书。 They are sitting in the shade of a tree.他们坐在树阴下乘凉。 He went in the rain to meet me at the station. 他冒雨到车站去接我。 the woman in white （black, red, yellow）穿着白（黑、红、黄）色衣服的妇女in uniform 穿着制服 将来时态in表以后 They will come back in 10 days 他们将10 天以后回来。
（一）介词概述 介词是一种虚词，在句子中不单独作任何句子成分。它是一种表示名词和句中其他词之间关系的词。它常和名词、动词、形容词等搭配，构成固定短语，表示不同意思。介词还可以与名词构成介词短语，表示方位、方向、时间、地点、方式、原因等。这些介词短语在句中可充当定语、状语、补语等。2000—2005年的中考中主要考了形容词与介词的搭配：如：be famous for；表示时间的介词，如：at night；动词与介词的搭配，如：arrive in/have dinner with sb.；表示方式、手段的介词，如：by phone/in English. （二）基础知识梳理 1．名词与介词的搭配 a bit of有一点儿 a couple of两个、几个 a kind of一种、一类cover an area of占地面积 have pity on sb.怜悯某人huge amounts of大量的 make friends with与……交朋友make fun of拿……开玩笑 meet the needs of迎合……的需要one after another一个接一个；连续地 play a trick on捉弄the week after next下下周 2．动词与介词的搭配 agree with sb.同意某人的意见apologize to sb. for sth.为某事向某人道歉arrive at/in a place到达某地ask for请求、寻求 be covered with被……所覆盖be made of由……制成 be made up of由……组成belong to属于 break into破门而人、闯入 call on拜访 care for照顾、喜欢carry out执行 check in办理登机come across被理解；遇见 come from出生于、来自come on跟我来、走吧
表示地点和位置的介词 1.at, in, on 1) at 表示较狭窄较小的地方（小村庄，小城镇），in 表示较大的地方（大城市，大的空间）。 I met her at the bus-stop. They arrived at the famous town in South Jiangsu. She is living in Nanjing. There are a great many islands in the Pacific. 2) 门牌号码前用at，road前面用on，street前用in或on。 in the street (BrE) on the street (AmE) at 103 Wall Street on the road 3) 把某个机构看成是机关或组织时用at，看成一个具体的地方时用in She is at Oxford. 她在牛津读书。She is in Oxford 她在牛津居住（工作或逗留） 4）at可以表示有意、有目的的行为。 She is at the table. 她在吃饭She is beside/ by the desk. 她坐在桌旁。 5) on 在---上面，表示上下两者紧贴在一起，in 表示在---里面。 She put the book on the desk. She put the book in the desk. She wore a smile on her face. (面部表情) She was wounded in the face. （伤有深度） 2．on 和underneath underneath 是on的反义词，表示某物紧贴在另一物的底下 There is a piece of paper underneath the dictionary. 3.under 和over under 和over 是一对反义词，表示正上方，正下方，没有接触的含义。 There are some chairs under the tree. The lamp hung over the table. under 和over 还可以表示上级、下级。 He is over us= We are under him. 4. above 和below 两者是一对反义词，表示高于、低于，既不表示接触，也不表示上下垂直。 The plane is flying above us. The sun has sunk below the horizon. 5. beneath 可以和underneath, under, below 互换。 6．at, by, beside at 表示有目的的接近、接触，by和beside 表示偶然的接近，不接触。 She will be waiting for you at the school gate at 7 tomorrow. The girl stood by/ beside her mother. To those who stand by me, I shall stand by my promise. 对那些支持我的人，我将恪守诺言。 7．near 和next to Near 表示在---附近，靠近；next to 表示紧挨着，紧靠着。 No birds or animals came near the lake. She went and sat next to him. 8. before, in front of, at the front of, ahead of before 用于某人前；in front of 用于建筑物前；in front of 和ahead of 用于空间可互换，用于时间只能用ahead of；in the front of 表示内部空间的前部；at the front of 表示外部空间
at, in与on的用法区别 1. 表示时间，注意以下用法： ①表示时间的某一点、某一时刻或年龄等用at： I get up at six in the morning. 我早上六点钟起床。 He got married at the age of 25. 他25 岁结婚。 ②泛指一般意义的上午、下午或晚上以及月或年等较长的时间，一般用in：We watch TV in the evening. 我们晚上看电视。 He went to Japan in 1946. 他于1946 去了日本。 ③若表示星期几或某一特定的日期，则用on： He left here on the fifth of May. 他于5 月5 日离开这儿。 2. 表示地点、场所、位置等，注意以下用法： ①表示某一点位置，用at： We live at No 87 Beijing Road. 我们住在北京路87 号。 The hospital is at the end of the street. 医院在这条街的尽头。 与名词所有格连用表示地点，也用at。如： at my sister’s 在我姐姐家 at the doctor’s 在医务室 ②表示空间或范围，用in： What’s in the box? 这盒子里有什么? He lives in Paris with his wife. 他同他妻子住在巴黎。 但有时两者可换用：
The meeting was held at [in] the hotel. 会议在宾馆举行。 ③at与in的另一个区别是：at多用于指较小的地方，而in多用于指较大的地方：in Shanghai 在上海at the station 在车站 ④介词on 用于地点，主要指在某物的表面： What’s on the table? 桌上有什么? There’s a wallet lying on the ground. 地上有个钱包。 【注】在少数搭配中，也用介词on： He works on a farm. 他在农场工作。 3. 在某些搭配中，三者的区别与英国英语和美国英语有关： in the street (英) / on the street (美) 在街上 in the road (英) / on the road (美) 在路上 in the team (英) / on the team (美) 在这个队 at the weekend (英) / on the weekend (美) 在周末 at weekends (英) / on weekends (美) 在周末 4. 有时三者的差别与搭配习惯和用法有关： in bed / on the bed 在床上 in the tree (多指树外之物) / on the tree (多指树本身之物) 在树上
英语中表示时间、地点和位置的常用介词的应用 内容摘要：介词是一种用来表示词与词, 词与句之间的关系的词,在句中不能单独作句子成分。介词后面一般有名词代词或相当于名词的其他词类、短语或从句作它的宾语。介词在英语中有非常重要的地位,但其种类繁多,用法复杂,一个介词还往往有多种意义,本文将从时间、地点和用名词尤其是由动词转化过来的名词的机会较多,而名词与名词之间常常需要介词连接,故英语中使用介词的现象比比皆是。 关键词:表示时间地点和位置附加状语名词动词 内容： 一、英语中表示时间的常用介词 after表示...之后，指某事发生在所指时间后的任意时间，是before的反义词，表示在...之后（1）用在附加状语里，常跟有-ing小句，，如： Li Ming was released from prison after serving three years.李明在服刑三年后出狱。（2）用在名词之后，如：I hate the time after sunset before you come home.我不喜欢日落之后、你回家之前的这段时间。（3）用在动词be之后，如：He turned and went after his brothers.他转身去追赶他的兄弟们。after通常指次序的先后。 in（1）表示在某世纪、年、季度、月、周”以及泛指的上、下午、晚上。如：in the 20th century在20世纪；in 1999在1999年；in winter在冬季；in September在九月；in the morning/afternoon/evening 在上午/下午/晚上。（2）in 过...后(未来时间)，不晚于，如：The train will arrive in three hours.火车三小时到。（3）表示某段时间之后，如：to return in a few minutes/hours/days/months几分钟/几小时/几天/几个月后回来。（4）表示做...时，...发生时，当...时，如：In attempting to save the child from drowning, she nearly lost her own life.她在抢救落水儿童时，自己差点丧命。 注：after与in都可表示“在……之后”，但after后可跟时间段，也可跟时间点；而in后必须跟时间段。after既可用于将来时，也可用于过去时，而in只能用于将来时。I’ll arrive in an hour. 我一小时后到。 during表示在……期间(1)某事在某段时间里连续发生或发生过几次，用在附加状语里，如：During all the years of work, he had been realistic with himself.这些年来在所有的工作中，他总是对自己实事求是。（2）表示某物在某段时间里从开始到结束，都一直得到发展，用在附加状语里，如:I hope this will become clear to you during the course of the lectures.我希望在讲座过程中，你会渐渐明白这一点。（3）指某事在某一期间内的某一刻发生，用在附加状语里，如：The boy disappeared from the hotel during the night.这名男孩在夜间从旅馆失踪。 from表示时间的起点，从……起，多用于“from…to/till…”中。如：You can come anytime from Monday to Friday. 周一至周五你什么时间来都行。from 仅说明什么时候开始，不说明某动作或情况持续多久。 for 表示达...之久（1）过了多少时间，后接“一段时间”，表示某事持续多久，多与完成时连用，如：She has been ill for several days. 她已经病了几天了。（2）表示某事已经发生过一次，用在附加状语里，如：Before using a pan for the first time, wash it with a sponge.在首次使用平底锅前，用
介词的用法 1.表示地点位置的介词 1)at ,in, on, to，for at (1)表示在小地方; (2)表示“在……附近，旁边” in (1)表示在大地方; (2)表示“在…范围之内”。 on 表示毗邻，接壤，“在……上面”。 to 表示在……范围外，不强调是否接壤；或“到……” 2)above, over, on 在……上 above 指在……上方,不强调是否垂直，与below相对； over指垂直的上方,与under相对,但over与物体有一定的空间，不直接接触。 on表示某物体上面并与之接触。 The bird is flying above my head. There is a bridge over the river. He put his watch on the desk. 3)below, under 在……下面 under表示在…正下方 below表示在……下，不一定在正下方 There is a cat under the table. Please write your name below the line. 4)in front [frant]of, in the front of在……前面 in front of…意思是“在……前面”，指甲物在乙物之前，两者互不包括；其反义词是behind（在……的后面）。There are some flowers in front of the house.(房子前面有些花卉。) in the front of 意思是“在…..的前部”，即甲物在乙物的内部.反义词是at the back of…（在……范围内的后部）。 There is a blackboard in the front of our classroom. 我们的教室前边有一块黑板。 Our teacher stands in the front of the classroom. 我们的老师站在教室前.(老师在教室里) 5）beside，behind beside 表示在……旁边 behind 表示在……后面 2.表示时间的介词 1)in , on，at 在……时 in表示较长时间，如世纪、朝代、时代、年、季节、月及一般（非特指）的早、中、晚等。 如in the 20th century, in the 1950s, in 1989, in summer, in January, in the morning, in one’s life , in one’s thirties等。 on表示具体某一天及其早、中、晚。 如on May 1st, on Monday, on New Year’s Day, on a cold night in January, on a fine morning, on Sunday afternoon等。 at表示某一时刻或较短暂的时间，或泛指圣诞节，复活节等。 如at 3:20, at this time of year, at the beginning of, at the end of …, at the age of …, at Christmas，at night, at noon, at this moment等。 注意：在last, next, this, that, some, every 等词之前一律不用介词。如：We meet every day. 2)in, after 在……之后 “in +段时间”表示将来的一段时间以后； “after+段时间”表示过去的一段时间以后； “after+将来的时间点”表示将来的某一时刻以后。 3)from, since 自从…… from仅说明什么时候开始，不说明某动作或情况持续多久；
英语地点介词的正确使用方法 地点介词主要有at ，in，on，to，above，over，below，under，beside，behind ，between。它们的用法具体如下： 1、at （1）at通常指小地方：In the afternoon，he finally arrived at home。到下午他终于到家了。 （2）at通常所指范围不太明显，表示“在……附近，旁边”：The ball is at the corner。球搁在角落里。 2、in （1）in通常指大地方：When I was young，I lived in Beijing。我小时候住在北京。 （2）在内部：There is a ball in in the box。盒子里有只球。 （3）表示“在…范围之内”（是从属关系）： Guangdong lies in the south of China。深圳在中国的南部。 3、on
（1）on主要指“在……之上”，强调和表面接触： There is a book on the table。桌上有一本书。 （2）表示毗邻，接壤（是相邻关系）： Canada lies on the north of America 加拿大在美国的北边（与美国接壤）。 4、to 主要表示“在……范围外”，强调不接壤，不相邻。 Japan is to the east of China。日本在中国的东面。 注意： （1）at 强调“点”，on 强调“面”，in 强调“在里面”，to 表示“范围外”。 （2）on the tree：表示树上本身所长着的叶子、花、果实等 in the tree：表示某物或某人在树上 on the wall：表示在墙的表面，如图画、黑板等 in the wall：表示在墙的内部中，如门窗、钉子、洞、孔 5、above
表示地点位置的介词 w qsa 1)at ,in, on, to，for at (1)表示在小地方; (2)表示“在……附近，旁边”in (1)表示在大地方; (2)表示“在…范围之内”。on 表示毗邻，接壤，“在……上面”。to 表示在……范围外，不强调是否接壤；或“到……”2)above, over, on 在……上above 指在……上方,不强调是否垂直，与below相对；over指垂直的上方,与under 相对,但over与物体有一定的空间，不直接接触。on表示某物体上面并与之接触。The bird is flying above my head. There is a bridge over the river. He put his watch on the desk. 3)below, under 在……下面under表示在…正下方below表示在……下，不一定在正下方There is a cat under the table. Please write your name below the line. 4)in front [frant]of, in the front of在……前面in front of…意思是“在……前面”，指甲物在乙物之前，两者互不包括；其反义词是behind（在……的后面）。There are some flowers in front of the house.(房子前面有些花卉。) in the front of 意思是“在…..的前部”，即甲物在乙物的内部.反义词是at the back of…（在……范围内的后部）。There is a blackboard in the front of our classroom. 我们的教室前边有一块黑板。Our teacher stands in the front of the classroom. 我们的老师站在教室前.(老师在教室里) 5）beside，behind beside 表示在……旁边behind 表示在……后面 2.表示时间的介词 1)in , on，at 在……时in表示较长时间，如世纪、朝代、时代、年、季节、月及一般（非特指）的早、中、晚等。如in the 20th century, in the 1950s, in 1989, in summer, in January, in the morning, in one’s life , in one’s thirties等。on表示具体某一天及其早、中、晚。如on May 1st, on Monday, on New Year’s Day, on a cold night in January, on a fine morning, on Sunday afternoon等。at表示某一时刻或较短暂的时间，或泛指圣诞节，复活节等。如at 3:20, at this time of year, at the beginning of, at the end of …, at the age of …, at Christmas，at night, at noon, at this moment等。注意：在last, next, this, that, some, every 等词之前一律不用介词。如：We meet every day. 2)in, after 在……之后“in +段时间”表示将来的一段时间以后；“after+段时间”表示过去的一段时间以后；“after+将来的时间点”表示将来的某一时刻以后。3)from, since 自从……from 仅说明什么时候开始，不说明某动作或情况持续多久；since表示某动作或情况持续至说话时刻，通常与完成时连用。since表示"自（某具体时间）以来"，常用作完成时态谓语的时间状语。since liberation（1980）自从解放（1980年）以来They have been close friends since childhood．他们从小就是好朋友。（1）since the war是指"自从战争结束以来"，若指"自从战争开始以来"，须说"since the beginning of the war"。（2）不要将since与after混淆。比较：He has worked here since 1965．（指一段时间，强调时间段）自从1965年以来，他一直在这儿工作。He began to work here after 1965．（指一点时间，强调时间点）从1965年以后，他开始在这儿工作。4)after, behind 在……之后after主要用于表示时间；behind主要用于表示位置。时间名词前介词用法口诀年前周前要用in 具体日子要用on 遇到几号也用on 上午下午得是in 要说某日上下午用on换in记清楚午夜黄昏用at 黎明用它也不错at用在时分前说“差”可要用上to 说"过''要用past 3.表示运动方向的介词： across, through 通过，穿过across表示横过,即从物体表面通过，与on有关，为二
第七单元介词 我们经常在名词或名词短语、代词或动名词前用介词表示人物、事件等与其它句子成分的关系。介词后面的名词或相当于名词的词语叫介词宾语。介词可表示地点、时间、比较、反对、原因、手段、所属、条件、让步、关于、对于、根据等。 二、介词的意义 1．表示时间的介词 in表示“在某一时间段”，或“在……某一时候”，如用在月、季、年份、时代、世纪等时间名词的前面，或用来泛指一天的某一段时间。 In July/summer/2000/ancient times/the 1999’s In the morning/afternoon/evening In也可以指“在……之后”，表示从说话起的若干时间内，如： The bus will be here in ten minutes. On表示“在特定的某一天”，也可用于带有修饰语的一天的某个时间段之前。如： on Saturday, on Saturday morning, on the morning of August 1st at表示“在某一时间点”，或用来表示不确定的时间和短期的假日、时节等。如： at six o’clock, at Easter 介词over, through (out)两者均指“经过的全部时间”。 Stay over the Christmas. 介词for, since for表示动作或状态延续的全部时间长度，为“长达……”之意；since用于指从过去特定的某个时刻到说话时为止的一段时间；两者往往用于完成时。 I have been there for six years. We have not seen each other since 1993. During指“在……时期/时间内”，必须以表示一段时间的词或词组作宾语。 She was ill for a week, and during that week she ate little. 2．表示地点的介词 介词at指小地点或集会场合；on表示线或面上的位置；in表示在立体、区域或环境内，特别是那些教大，能够容纳相应事物的环境。 He works at Peking University. Your radio is on the desk. The boat is in the lake. 3．表示原因的介词 for常常表示褒贬、奖惩的原因或心理原因。 4．表示目的的介词 for表示拟定的接收人或目的；to表示实际的接收人或目的。 I bought the gift for my little sister. I gave the gift to my little sister. 5．表示“关于……”的介词 一般about用于比较随便的谈话或非正式的文体；on用于正式的讲话、著作或报告中；7．表示价格的介词 at和for都可表示价格，at仅表示价格，for还表示“交换”，如： Eggs are sold at 95 cents a dozen here. I bought it for five pounds.
具体日期前用“on” 注意: 一、含有this, that, these, those, every, each 等的时间状语前不用介词。如： We are going to play football this afternoon. 今天下午我们打算踢足球。 His father goes to work early every day. 他爸爸每天很早去上班。They are working on the farm at the moment. 这几天他们正在农场干活。 二、all day, all week, all year 等由“all +表示时间的名词”构成的时间状语前不用介词。如： We stay at home and watch TV all day.我们整天呆在家里看电视。 三、由“some, any, one等＋表示时间的名词”构成的时间状语前不用介词。如： We can go to the Great Wall some day. 有一天我们会去长城的。 四、时间状语是today, tomorrow, tomorrow morning, tomorrow afternoon, tomorrow evening, the day after tomorrow (后天)等，其前不用介词。如：
What day is it today?今天星期几？ Who's on duty tomorrow? 明天谁值日？ MORE: at 表示时间的某一点 （节日或年龄、瞬间或短暂的时间） Your memory is always poor at this time. （表示一天中的某个时刻不用冠词） I got up at six in the mopning. on 表示某日或和某日连用的某个时间段 You were late on Monday last week. in 用于表示除日以外的某一时间段 （表示年、月、季节、世纪时代） Sorry, I am late, the frist time in May. in和at都可表示地点，而in表示的地点比at所表示的地点大
表示地点位置的介词 1)at ,in, on, to at (1)表示在小地方; (2)表示“在……附近，旁边”in (1)表示在大地方; (2)表示“在…范围之内”。on 表示毗邻，接壤，“在……上面”。 to 表示在……范围外，不强调是否接壤；或“到……” 2)above, over, on 在……上 above 指在……上方,不强调是否垂直，与below相对； over指垂直的上方,与under相对,但over与物体有一定的空间，不直接接触。 on表示某物体上面并与之接触。 The bird is flying above my head. There is a bridge over the river. He put his watch on the desk. 3)below, under 在……下面 under表示在…正下方 below表示在……下，不一定在正下方 There is a cat under the table. Please write your name below the line. 4)in front of, in the front of在……前面 in front of…意思是“在……前面”，指甲物在乙物之前，两者互不包括；其反义词是behind （在……的后面）。 There are some flowers in front of the house.(房子前面有些花卉。) in the front of 意思是“在…..的前部”，即甲物在乙物的内部.反义词是at the back of…（在……范围内的后部）。There is a blackboard in the front of our classroom. 我们的教室前边有一块黑板。Our teacher stands in the front of the classroom. 我们的老师站在教室前.(老师在教室里) 5）beside，behind beside 表示在……旁边 behind 表示在……后面 2.表示时间的介词 1)in , on，at 在……时 in表示较长时间，如世纪、朝代、时代、年、季节、月及一般（非特指）的早、中、晚等。 如in the 20th century, in the 1950s, in 1989, in summer, in January, in the morning, in one’s life , in one’s thirties等。 on表示具体某一天及其早、中、晚。 如on May 1st, on Monday, on New Year’s Day, on a cold night in January, on a fine morning, on Sunday afternoon等。 at表示某一时刻或较短暂的时间，或泛指圣诞节，复活节等。如at 3:20, at this time of year, at the beginning of, at the end of …, at the age