Glycerol, propoxylated, esters with acrylic acid

Carcinogenicity

Description of key information

The substance was observed to be non-carcinogenic in male C3H/HeJ mice after dermal application of 25 µL10% v/v in acetone twice daily for 94 weeks (Cytec, 1987). However, the study design is outdated and the study is rated as less reliable and only used as supportive information.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Link to relevant study records

Reference

Endpoint:

carcinogenicity: dermal

Type of information:

experimental study

Adequacy of study:

other information

Study period:

From September 10, 1984 to June 28, 1986

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

significant methodological deficiencies

Remarks:

Study well documented, meets generally accepted scientific standards but study design is outdated. Therefore study is rated as less reliable and only used as supportive information.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Groups of male C3H/HeJ mice (50/dose) were topically treated with 25 µL of 10 % v/v test item in acetone, twice weekly for 94 weeks. The skin from all animals was examined histologically for non-neoplastic and neoplastic lesions. Histological examination of internal organs was performed on one half of the mice of each group.

GLP compliance:

not specified

Species:

mouse

Strain:

other: C3H/HeJ

Sex:

male

Route of administration:

dermal

Vehicle:

other: Acetone and deionized water

Details on exposure:

TEST MATERIAL
- Amount(s) applied: 25 µL
- Concentration: 10% glycerol propoxylate triacrylate in acetone

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

94 weeks

Frequency of treatment:

Twice/week

Post exposure period:

No

Dose / conc.:

10 other: %

Remarks:

v/v in acetone (nominal conc.)

No. of animals per sex per dose:

50

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Doses were selected on the basis of a pilot study

Positive control:

0.025 % benzo(a)pyrene (BaP) in acetone

Observations and examinations performed and frequency:

DERMAL IRRITATION: Yes

BODY WEIGHT: Yes

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see Tables Ce 84-1-14)

HISTOPATHOLOGY: Yes (see Tables 1-42)
- Skin from the application sites of all mice, all skin tumors and suspected skin lesions were examined histologically
- Internal organs and tissues of 25 mice/group, randomly selected, were examined microscopically

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
- Survival (%): 100, 92, 86, 76, 54, 44 and 30 recorded at 13, 26, 39, 52, 65, 78 and 91 weeks, respectively
- No significant signs of toxicity

BODY WEIGHT AND WEIGHT GAIN
- No significant difference between body weight gains between test and control groups

HISTOPATHOLOGY: NEOPLASTIC/ NON-NEOPLASTIC:

SKIN
- Blank and vehicle control: Slight or moderate degree non-neoplastic lesions; fibrosis of the dermis and acanthosis, keratosis and hyperplasia of the epidermis; no skin neoplasms
- Treatment group (C-663): Moderate fibrosis of the dermis with scar formation, moderate degree of acanthosis and keratosis of the epidermis with dysplastic changes; papillary hyperplasia; no skin neoplasms

INTERNAL ORGANS
- Blank control: Moderate to severe urinary tract infection and prostatitis; myocarditis and slight to moderate pneumonia; age-related atrophy of the testes, lymphocytic lymphoma (in 1 mouse) and hepatocellular carcinoma (in 6 mice)
- Vehicle control: Prostate and urinary tract infections; age-related atrophy of testis (in 9 mice) and hepatocellular carcinoma (in 7 mice)
- Treatment group (C-663): Lung, urinary tract and prostate infections; lymphocytic lymphoma (in 1 mice), hepatocellular carcinomas (in 8 mice) and angioma in the liver (in 1 mouse)

Relevance of carcinogenic effects / potential:

Incidence of carcinomas in animals treated with test item were within the range of those detected in historical control animals for C3H/HeJ strain of mice

Dose descriptor:

dose level: 10 % v/v in acetone

Effect level:

10 other: %

Based on:

test mat.

Sex:

male

Basis for effect level:

histopathology: neoplastic

Key result

Critical effects observed:

no

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

19.5 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No 1272/2008

Based on the available data, classification for carcinogencity is not triggerd according to Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.

Additional information

There are no valid experimental data available to assess the carcinogenicity of the test substance. Nevertheless, a less reliable study is available delivering supportive information for weigh of evidence approaches.

Studies according to other protocols:

A study (Cytec, 1987) was conducted to assess the carcinogenic potential and chronic dermal toxicity of GPOTA in male C3H/HeJ mice. Therefore groups of male C3H/HeJ mice (50/dose) were topically treated with 25 µL of 10 % v/v GPOTA in acetone, twice weekly for 94 weeks. The dose and concentration of each material were selected after completion of a pilot study. Control animals received no treatment or 50 µL of acetone twice weekly. Positive control group received 50 µL twice weekly of 0.025 % benzo(a)pyrene (BaP) in acetone. The skin from all animals was examined histological for non-neoplastic and neoplastic lesions. Histological examination of internal organs was performed on one half of the mice of each group. Survival (%) in mice treated with GPOTA was calculated to be 100, 92, 86, 76, 54, 44 and 30 at 13, 26, 39, 52, 65, 78 and 91 weeks, respectively. No significant difference between body weight gains was observed between test and control groups. Moderate fibrosis of the dermis with scar formation, moderate degree of acanthosis and keratosis of the epidermis with dysplastic changes; papillary hyperplasia were observed at application sites. Skin neoplasms were not observed. Examination of internal organs revealed no treatment related lesions. Pathological examination revealed lung, urinary tract and prostate infections; lymphocytic lymphoma (in 1 mice), hepatocellular carcinomas (in 8 mice) and angioma in the liver (in 1 mouse). In conclusion, GPOTA was not carcinogenic in male C3H/HeJ mice. (Applicant calculation of application per day: 1000/30 (correction bw) * 25 µL * 0.1 (concentration) 0.82 g/cm3 (density correction 20 µL TI + 180 µL Aceton (ideal calculated))) * 2/7 (two time per week application without depot)=19.5 mg/kg bw/day).

Assessment of in vivo carcinogenicity:

As no concern for carcinogenic potential is derived from the genetic toxicity tests, and a less reliable but negative carcinogenicity test with mice shows also no evidence for dermal carcinogenicity of GPOTA no increased carcinogenic potential is suspected. No further tests are proposed on this information.