Sulphuric acid, compound with graphite

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

Type of information:

migrated information: read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study has been performed according to internationally accepted testing guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: OECD Guideline 422 "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test" (March 1996)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

not applicable

Molecular formula:

not applicable

IUPAC Name:

not applicable

Details on test material:

Expanded Graphite Powder

Test animals

Species:

rat

Strain:

Wistar

Administration / exposure

Route of administration:

oral: feed

Vehicle:

not specified

Analytical verification of doses or concentrations:

yes

Details on mating procedure:

Animals were mated beginning after two weeks of treatment for two consecutive weeks or until successful mating. Overnight mating was performed 1 male : 1 female of the same dose group. Vaginal smears were taken the next morning. Mating was considered successful if sperm and/or a vaginal plug was found. The day of finding sperm was considered day 0 p.c. Time to successful insemination (precoital time) was determined.

Duration of treatment / exposure:

Animals were inspected at least once daily and the individual body weight and food consumption of all animals was recorded weekly until sacrifice of the animalsAfter successful mating (day of finding sperm in vaginal smears = day 0 post conceptionem [p.c.]), treatment of the females was continued until day 4 post partum (p.p., day of birth = day 0 p.p.) and subsequent sacrifice. Treatment of all males and females not successfully mated was continued until their sacrifice.

No. of animals per sex per dose:

The study commenced with 40 male and 40 female rats

Control animals:

yes

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Remarks:

parental, reproductive and developmental

Effect level:

12 000 mg/kg diet

Based on:

test mat.

Basis for effect level:

other: maternal and developmental toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

12 000 mg/kg diet

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: developmental toxicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

None of the sporadically observed clinical findings were regarded as test item related. No effects of test item exposure were observed on body weight, body weight gain or food consumption of the animals at any time point of the study. Overall, haematological and clinical chemistry data were found to be in the ranges expected for the species, strain, sex and age. Therefore, sporadical findings, albeit significantly different from controls in individual cases, are considered to be of no toxicological relevance. No effects of test item exposure were observed on locomotor activity, neither for any of the investigated time intervals, nor for the whole test period. No effects of test item exposure were observed on any of the investigated endpoints of the Functional Observational Battery.

For investigation of mating data, each group consisted of 20 pairs for mating. For the four groups, mating yielded 19, 19, 20, and 18 sperm positive females, in groups 1-4, respectively. This resulted in 14, 10, 13, and 10 pregnancies; 11, 9, 13, and 10 females with liveborn offspring in F0 dams, and 11, 9, 12, and 10 females with live litters on day 4 p.p., respectively.

The results show that mating outcome throughout all groups including control groups in both mating subsets was insufficient. The reasons for this phenomenon are unclear. However, no effect of the test item exposure was observed on any of the investigated endpoints like precoital time or fertility (number of mated females, number of pregnant females, number of implantation sites, number of liveborn pups). No effect of the test item exposure could be observed on litter size and pup survival as well as pup body weight. None of the sporadically observed clinical findings in pups were considered test item related and no abnormal pups were observed. The main necropsy findings consisted in reduced size of testes and epidydimides, which were found in all groups including the control group. Sporadically observed statistically significant differences in organ weights were not considered an adverse effect of the test item exposure. Substance-related findings were not observed in the histologically examined organs of males and females of the control and high dose group.

Applicant's summary and conclusion

Conclusions:

Based on the results described above, the NOAEL for this study (parental, reproductive and developmental) was determined as the high (limit) target dose level of 12.000 mg/kg food (11.500 mg/kg food as determined by chemical analysis).

Executive summary:

The aim of this study was to evaluate possible adverse effects of Expanded Graphite Powder after repeated exposure especially on male and female reproductive performance, such as gonadal function, mating behaviour, conception, development of the conceptus and parturition after exposure via food. The study was conducted following the OECD Guideline 422 "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test" (March 1996).

Based on the results described above, the NOAEL for this study (parental, reproductive and developmental) was determined as the high (limit) target dose level of 12.000 mg/kg food (11.500 mg/kg food as determined by chemical analysis). This corresponds to the following actual substance intake: 813 mg/kg body weight/day for males; 1067 mg/kg body weight/day for females in the premating period, 930 mg/kg body weight/day for females during gestation and 1159 mg/kg body weight/day for females during lactation, respectively.