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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Justification for type of information:
Data is from peer-reviewed journal.

Data source

Reference
Reference Type:
publication
Title:
Evaluation of the teratogenic potential of the Oxidative dyes 6-chloro-4-nitro-2-aminophenol And o-chloro-p-phenylenediamine
Author:
J. C. PICCIANO, W. E. MORRIS and B. A. WOLF
Year:
1984
Bibliographic source:
Fd Chem. Toxic. Vol. 22, no. 2, pp. I47 149, 1984

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
The present study was conducted to determine the teratogenic potential of 2-chloro-p-phenylenediamine (o-chloro-p-PD) (CAS No.- 615-66 -7).
GLP compliance:
not specified

Test material

Constituent 1
Chemical structure
Reference substance name:
2-chloro-p-phenylenediamine
EC Number:
210-441-2
EC Name:
2-chloro-p-phenylenediamine
Cas Number:
615-66-7
Molecular formula:
C6H7ClN2
IUPAC Name:
2-chlorobenzene-1,4-diamine
Details on test material:
- Name of test material (as cited in study report): o-chloro-p-phenylenediamine (o-chloro-p-PD)
- Molecular formula (if other than submission substance): C6H7N2Cl
- Molecular weight (if other than submission substance): 142.59 g/mole
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations): No data available
Specific details on test material used for the study:
- Name of test material (as cited in study report): 2-chloro-p-phenylenediamine (o-chloro-p-PD)
- Molecular formula: C6H7N2Cl
- Molecular weight:142.59 g/mole
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations):No data available

Test animals

Species:
rat
Strain:
Sprague-Dawley
Details on test animals or test system and environmental conditions:
Sex: Female

Administration / exposure

Route of administration:
oral: gavage
Type of inhalation exposure (if applicable):
not specified
Vehicle:
propylene glycol
Details on exposure:
PREPARATION OF DOSING SOLUTIONS: o-chloro-p-phenylenediamine was dissolved in propylene glycol before administration.

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): Propylene glycol
- Concentration in vehicle: 0, 100, 200 and 400 mg/kg/day
- Amount of vehicle (if gavage): 10 ml/kg
- Lot/batch no. (if required): No data available
- Purity: No data available
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
- M/F ratio per cage:1 : 2 ratio
- Length of cohabitation:No data available
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy:Sperm plug or the presence of sperm in a vaginal smear referred to as day 0 of pregnancy.
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. No data available
- Further matings after two unsuccessful attempts: [no / yes (explain)]:No data available
- After successful mating each pregnant female was caged (how): Caged separately
- Any other deviations from standard protocol: No data available
Duration of treatment / exposure:
10 days
Frequency of treatment:
Daily
Duration of test:
10 days
Doses / concentrations
Remarks:
Doses / Concentrations:
0,100, 200 and 400 mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
Total : 53
10 ml/kg : 20 female
100 mg/kg/day : 11 female
200 mg/kg/day : 11 female
400 mg/kg/day : 11 female

Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
Mortality , general health and condition and body weight and gross abnormalities were examined
Ovaries and uterine content:
Number of implantation sites and number of resorptions were also examined.
Fetal examinations:
Litter was observed for survival rate, body weight, number of litter, sex ratio, general appearance, Gross, visceral and skeletal anomalies in fetuses were observed.
Statistics:
Weight changes, the number of fetal implantations, fetal weights and the fetal sex ratio were analyzed by using Student's t test, The numbers of foetal resorptions and abnormal foetuses were compared by chi square analysis and vehicle control data were combined after an analysis of variance.
Indices:
Fertility index, gestation index, delivery index and implantation index were examined.
Historical control data:
No data available

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Clinical signs:
no effects observed
Description (incidence and severity):
No abmormalities were observed in treated female rats
Dermal irritation (if dermal study):
not specified
Mortality:
no mortality observed
Description (incidence):
No mortality were observed in treated female rats
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Mean weight gain was decreased on 6-16 day in 200 mg/kg/day and on 6-20 day in 400 mg/kg/day treated female rats.
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
Behaviour (functional findings):
not specified
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified
Details on results:
Reproductive function:
No change were observed in fertility index, gestation index and implantation index of treated female rat as compare to control.

Statistically significant increase in the number of resorptions were observed in 400 mg/kg/day treated rats

Reproductive performance:
No effect were observed on reproductive performance of treated animals as compare to control.

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
Mortality :
No mortality were observed in treated female rats

Clinical signs:
No abmormalities were observed in treated female rats

Body weight and weight gain:
Mean weight gain was decreased on 6-16 day in 200 mg/kg/day and on 6-20 day in 400 mg/kg/day treated female rats.

Reproductive function:
No change were observed in fertility index, gestation index and implantation index of treated female rat as compare to control.

Statistically significant increase in the number of resorptions were observed in 400 mg/kg/day treated rats

Reproductive performance:
No effect were observed on reproductive performance of treated animals as compare to control.


Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: No adverse effect on survival, clinical sign, body weight, reproductive performance.

Maternal abnormalities

Abnormalities:
not specified

Results (fetuses)

Fetal body weight changes:
effects observed, treatment-related
Description (incidence and severity):
Weight of both male and female fetuses were significantly decreased as compare to control
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): not specified
Reduction in number of live offspring:
not specified
Changes in sex ratio:
no effects observed
Description (incidence and severity):
No significant differences in the male and female sex ratio of fetuses were observed as compare to control
Changes in litter size and weights:
not specified
Changes in postnatal survival:
not specified
External malformations:
no effects observed
Description (incidence and severity):
No significant differences were observed in number of abnormal foetuses and the types of gross anomalies in treated female rat as compare to contol.
Skeletal malformations:
no effects observed
Description (incidence and severity):
No significant differences were observed in number of abnormal foetuses and the types of skeletal anomalies in treated female rat as compare to contol.
Visceral malformations:
no effects observed
Description (incidence and severity):
No significant differences were observed in number of abnormal foetuses and the types of visceral anomalies in treated female rat as compare to contol.
Other effects:
not specified
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects: no effects

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
200 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
NOAEL was considered to be 100 mg/kg/day for maternal study and 200 mg/kg/day for teratogenicity study when female rat were exposed to 2-chloro-p-phenylenediamine (o-chloro-p-PD).
Executive summary:

In a teratogenicity study, female Sprague-Dawley rat were exposed to 2-chloro-p-phenylenedia mine (o-chloro-p-PD) orally in the concentration of 0, 100, 200 and 400 mg/kg/day. In the parental generation, decreased in mean body weight were observed in 200 and 400 mg/kg/day treated rat as compared to control . In addition,significant increase in the number of resorptions were observed in female rat. Effect on male and female fetal weight was observed when treated with 400 mg/kg/day. Therefore, NOAEL was considered to be 100 mg/kg/day for maternal study and 200 mg/kg/day for teratogenicity study when rats are exposed to 2-chloro-p-phenylenediamine (o-chloro-p-PD) orally for 10 days.