Benzene-1,4-diammonium sulphate

Toxicity to reproduction

Administrative data

Endpoint:

reproductive toxicity, other

Remarks:

Teratogenicity

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Remarks:

experimental data of read across substances

Justification for type of information:

Data for the target chemical is summarized based on the structurally similar read across chemicals

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

Final Report on the Safety Assessment of Toluene=2,5Diamine, Toluene-2,5 -Diami ne Sulfate, and Toluene-3,4-Diamine

Author:

COSMETIC INGREDIENT REVIEW

Year:

1992

Bibliographic source:

Journal of the American College of Toxicology Volume 1 1, Number 4,1992

Reference 2

Reference Type:

secondary source

Title:

Opinion on: Toluene-2,5-diamine

Author:

European Commission (EC) - Scientific Committee on Consumer Products (SCCP)

Year:

2007

Bibliographic source:

the Scientific Committee on Consumer Products, SCCP/1084/07

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: As mentioned below

Principles of method if other than guideline:

Reproductive and developmental toxicity study test chemical was performed on New Zealand White Rabbit

GLP compliance:

not specified

Limit test:

no

Justification for study design:

No data available

Test material

Test material information

Constituent 1

Reference substance name:

2-methyl-p-phenylenediamine sulfate

EC Number:

210-431-8

EC Name:

2-methyl-p-phenylenediamine sulfate

Cas Number:

615-50-9

Molecular formula:

C7H10N2.H2O4S

IUPAC Name:

2-methyl-p-phenylenediamine sulfate

Test material form:

solid: particulate/powder

Details on test material:

-IUPAC name:2-methyl-p-phenylenediamine sulphate- Name of test material : Toluene-2,5-diamine sulphate- Molecular formula : C7H12N2O4S- Molecular weight : 220.2478 g/mol- Substance type: Organic- Physical state: Off-white powderInChI:1S/C7H10N2.H2O4S/c1-5-4-6(8)2-3-7(5)9;1-5(2,3)4/h2-4H,8-9H2,1H3;(H2,1,2,3,4)Smiles:Cc1cc(ccc1N)N.OS(=O)(=O)O

Specific details on test material used for the study:

RA CAS no : 615-50-9Study reference: Title: Opinion on: Toluene-2,5-diamineFinal Report on the Safety Assessment of Toluene=2,5Diamine, Toluene-2,5 -Diami ne Sulfate, andToluene-3,4-DiamineAuthor: European Commission (EC) - Scientific Committee on Consumer Products (SCCP)COSMETIC INGREDIENT REVIEWBibliographic source: the Scientific Committee on Consumer Products, SCCP/1084/07Journal of the American College of ToxicologyVolume 1 1, Number 4,1992

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on species / strain selection:

No data available

Sex:

female

Details on test animals or test system and environmental conditions:

No data available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled water

Details on exposure:

Details on exposurePREPARATION OF DOSING SOLUTIONS: test material dissolved in distilled water DIET PREPARATION- Rate of preparation of diet (frequency):No data available- Mixing appropriate amounts with (Type of food )- Storage temperature of food: No data availableVEHICLE- Justification for use and choice of vehicle (if other than water): - Concentration in vehicle: 0, 10, 25, 50 mg/kg bw/d, - Amount of vehicle (if gavage): No data available- Lot/batch no. (if required): No data available- Purity: No data available

Details on mating procedure:

- M/F ratio per cage:No data available - Length of cohabitation: No data available - Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancyNo data available - 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): No data available - Any other deviations from standard protocol:The females were fertilised by natural mating. After coitus HCG was given i.v. to ensure ovulation.

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

12 days (from day 6 to 18 of gestation)

Frequency of treatment:

once daily

Details on study schedule:

No data available

Doses / concentrations

Remarks:

0, 10, 25, 50 mg/kg bw/d,

No. of animals per sex per dose:

Total:820 mg/kg bw/day:1610mg/kg bw/day:1625mg/kg bw/day:1650 mg/kg bw/day:16Positive control group:18

Control animals:

yes, concurrent vehicle

Details on study design:

No data available

Positive control:

No data available

Examinations

Parental animals: Observations and examinations:

Parental animals observation and examinationsCAGE SIDE OBSERVATIONS: yes DETAILED CLINICAL OBSERVATIONS: Yes Time schedule: daily BODY WEIGHT: YesTime schedule for examinations: The body weights were determined on days 0, 6, 18 and 28 of gestation.FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes / No / No data: No data availableWATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data Time schedule for examinations: OTHER:

Oestrous cyclicity (parental animals):

No data available

Sperm parameters (parental animals):

No data available

Litter observations:

No data available

Postmortem examinations (parental animals):

Postmortem examinations (Parent Animal)SACRIFICE :On day 28 of gestation the animals were sacrificed,Male animals: All surviving animals [describe when, e.g. as soon as possible after the last litters in each generation were produced.]: No dataMaternal animals: yes All surviving animals [describe when, e.g. after the last litter of each generation was weaned :GROSS NECROPSY: No data available HISTOPATHOLOGY / ORGAN WEIGHTSThe tissues indicated in Table [#] were prepared for microscopic examination and weighed, respectively.: macroscopic examination was performed

Postmortem examinations (offspring):

Postmortem examinations (offspring)SACRIFICE- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at [#?] days of age.- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: the foetuses were dissected and examined for congenital abnormalities and macroscopic changes. The common section parameters were recorded. Half of the foetuses were examined for skeletal and the other half for visceral abnormalities.

Statistics:

No data available

Reproductive indices:

No data available

Offspring viability indices:

No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Description (incidence and severity):

No clinical signs were observed.

Dermal irritation (if dermal study):

not specified

Mortality:

mortality observed, non-treatment-related

Description (incidence):

1 female at 10 and 1 female at 25 mg/kg bw/d died, at 50 mg/kg 3 females died presumably because of the intubation procedure.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

Body weights of the females in the dose groups were similar to the controls.

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

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

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

Remarks on result:

other: No effects on reproductive performance

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:

no mortality observed

Description (incidence and severity):

The number of the foetuses were not influenced by substance treatment

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The foetal body weights were not influenced by substance treatment

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):

The frequencies of external abnormalities, visceral malformations and variations as well as skeletal defects exhibited no substance-related changes.

Histopathological findings:

not specified

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:

50 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

viability

mortality

body weight and weight gain

gross pathology

Remarks on result:

other: no effects on overall developmental parameters

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:

No Observed Adverse Effect Level (NOAEL) for maternal toxicity and embryotoxicity was considered to be 50 mg/kg/day. When female New Zealand White Rabbit were treated with test chemical orally from day 6 to 18 of gestation.

Executive summary:

The reproductive and developmental toxicity study of test chemical was performed in female New Zealand White Rabbit. The test material dissolved in distilled water and administered in dose concentration 0, 10, 25, 50 mg/kg bw/d, by oral gavage route from day 6 to 18 of gestation while positive control Vitamin A in rape seed oil in dose concentration 6 mg/kg bw/d given by same route. The females were fertilised by natural mating. After coitus HCG was given i.v. to ensure ovulation. The animals were examined daily for mortality and clinical signs. The body weights were determined on days 0, 6, 18 and 28 of gestation. On day 28 of gestation the animals were sacrificed, the foetuses were dissected and examined for congenital abnormalities and macroscopic changes. The common section parameters were recorded. Half of the foetuses were examined for skeletal and the other half for visceral abnormalities. 1 female at 10 and 1 female at 25 mg/kg bw/d died, at 50 mg/kg 3 females died presumably because of the intubation procedure. No clinical signs were observed. Body weights of the females in the dose groups were similar to the controls. The changes in the incidences of intrauterine death observed were not dose-related. The number and sex of the foetuses as well as the foetal body weights were not influenced by substance treatment. The frequencies of external abnormalities, visceral malformations and variations as well as skeletal defects exhibited no substance-related changes. The positive control (Vitamin A) did not show teratogenicity and only slight embryotoxicity. Hence No Observed Adverse Effect Level (NOAEL) for maternal toxicity and embryotoxicity was considered to be 50 mg/kg/day. When female New Zealand White Rabbit were treated with test chemical orally from day 6 to 18 of gestation.