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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
one-generation reproductive toxicity
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Justification for type of information:
Data is from European Commission, NTRL and OECD SIDS

Data source

Referenceopen allclose all

Reference Type:
secondary source
Title:
Reproductive toxicity study of CAS no 100-21-0
Author:
European Commission
Year:
2000
Bibliographic source:
European Commission – European Chemicals Bureau, 22–FEB–2000
Reference Type:
secondary source
Title:
A ninety day study of treephthalic acid (CAS no 100-21-0) ininduced urolithiasis and reproductive performance in westar and CD rats
Author:
NTRL
Year:
1982
Bibliographic source:
National Technical Reports Library (NTRL), OTS94820190, 1982
Reference Type:
secondary source
Title:
SIDS Initial Assessment Report of Terephthalic Acid (TPA)
Author:
OECD SIDS
Year:
2001
Bibliographic source:
OECD SIDS, 2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: as below
Principles of method if other than guideline:
One-generation reproduction toxicity study of Terephtalic acid in Rats
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
Name of the test chemical:Terephthalic acid
Molecular Formula:C8H6O4
Molecular Weight:166.131 g/mol
SMILES notation: c1(C(O)=O)ccc(C(O)=O)cc1
Substance Type:Organic
Physical State: Solid
Specific details on test material used for the study:
Name of the test chemical:Terephthalic acid
Molecular Formula:C8H6O4
Molecular Weight:166.131 g/mole
SMILES notation: c1(C(O)=O)ccc(C(O)=O)cc1
Substance Type:Organic
Physical State: Solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
- Housing: Female were housing in a solid bottom cage

Administration / exposure

Route of administration:
oral: feed
Type of inhalation exposure (if applicable):
not specified
Vehicle:
other: feed
Details on mating procedure:
- M/F ratio per cage: 1:1
- Length of cohabitation: Two weeks
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 Days
Frequency of treatment:
Daily
Details on study schedule:
not specified
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day
Dose / conc.:
15 mg/kg bw/day
Dose / conc.:
62.5 mg/kg bw/day
Dose / conc.:
250 mg/kg bw/day
Dose / conc.:
1 000 mg/kg bw/day
Dose / conc.:
2 500 mg/kg bw/day
No. of animals per sex per dose:
Total: 120
0 mg/kg/day: 10 male, 10 female
15 mg/kg/day: 10 male, 10 female
62.5 mg/kg/day: 10 male, 10 female
250 mg/kg/day: 10 male, 10 female
1000 mg/kg/day: 10 male, 10 female
2500 mg/kg/day: 10 male, 10 female
Control animals:
yes, concurrent vehicle
Details on study design:
Not specified
Positive control:
Not specified

Examinations

Parental animals: Observations and examinations:
Survival, Clinical sign, Body weight and weight gain, food consumption were examined.
Oestrous cyclicity (parental animals):
Not specified
Sperm parameters (parental animals):
Not specified
Litter observations:
Pup viability, body weight and sex distribution were examined
Postmortem examinations (parental animals):
Gross pathology was examined.
Postmortem examinations (offspring):
Gross pathology and histopathology was examined.
Statistics:
Not specified
Reproductive indices:
Mating performance, fertility index, lit.ter size, mating, gestation, lactation and post weaning periods was examined.
Offspring viability indices:
Yes

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
Diarrhea was observed in some of the rats at 2500 mg/kg bw
Dermal irritation (if dermal study):
not specified
Mortality:
mortality observed, treatment-related
Description (incidence):
Five unscheduled deaths occurred between 4 and 13 weeks in animls at 2500 mg/kg bw
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Dose-related decreases in body weight and weight gain were observed in all dose groups.
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Dose-related decreases in food consumption were observed in all dose groups.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
Description (incidence and severity):
No effect on fertility and litter size were observed in treated rats.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
reproductive performance
Remarks on result:
other: No effect observed

Target system / organ toxicity (P0)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
Decrease in pup viability were observed at 1000 and 2500 mg/kg bw
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Significant decrease in body weight of pups were observed at 2500 mg/kg bw
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Description (incidence and severity):
No gross anomalies were observed in pups.
Histopathological findings:
no effects observed
Description (incidence and severity):
No foetal malformations were observed.
Other effects:
not specified

Developmental neurotoxicity (F1)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F1)

Developmental immunotoxicity:
not specified

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
250 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
viability
mortality
body weight and weight gain
gross pathology
histopathology: non-neoplastic
Remarks on result:
other: No effect observed

Target system / organ toxicity (F1)

Critical effects observed:
not specified
System:
other: not specified
Organ:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 1000 mg/kg bw for P and 250 mg/kg bw for F1 generation when male and female Wistar rats were treated with Terephtalic acid orally in feed for 90 days.
Executive summary:

In a One-generation reproduction toxicity study, Wistar male and female rats treated with Terephtalic acid in the concentration of 0, 15, 62.5, 250, 1000 and 2500 mg/kg/day orally in feed for 90 days. Diarrhea was observed in some of the rats at 2500 mg/kg bw. Five unscheduled deaths occurred between 4 and 13 weeks in animals at 2500 mg/kg bw. Dose-related decreases in body weight and weight gain and food consumption were observed in all dose groups. No effect on reproductive parameters such as fertility and litter size were observed in treated rats. No bladder stones were observed in dead animals. In addition, Decrease in pup viability and Significant decrease in body weight were observed at 1000 and 2500 mg/kg bw. No gross anomalies and fetal malformations were observed. Therefore, NOAEL was considered to be 1000 mg/kg bw for P and 250 mg/kg bw for F1 generation when male and female Wistar rats were treated with Terephtalic acid orally in feed for 90 days.