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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
screening for reproductive / developmental toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
1999
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Data are based on secondary sources of p-Toluenesulfonamide, which is the metabolite of Chloramine T. Based on the comparable structural, physicochemical and toxicological profile, it can be used as read across substance.
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2002
Reference Type:
secondary source
Title:
Unnamed
Year:
1999

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Combined Repeated Dose and Reproductive / Developmental Toxicity Screening Test (Precursor Protocol of GL 422)
Deviations:
not specified
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): para-Toluenesulfonamide
- Molecular formula: C7-H9-N-O2-S
- Molecular weight: 171.22
- Smiles notation: S(=O)(=O)(c1ccc(cc1)C)N
- InChl: 1S/C7H9NO2S/c1-6-2-4-7(5-3-6)11(8,9)10/h2-5H,1H3,(H2,8,9,10)
- Structural formula attached as image file (if other than submission substance): See Fig.
- Substance type: Aromatic sulfonamide
- Physical state: White, solid crystalline powder
- Purity: 99.9%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
Formulation in 5% gum Arabic solution
Duration of treatment / exposure:
Males: 42 days before mating
Females: from 14 days before mating, throughout gestation in females and up to day 3 of lactation.
Frequency of treatment:
Daily
Doses / concentrations
Remarks:
Doses / Concentrations:
120, 300 and 750 mg/kg bw/day
Basis:
actual ingested
Control animals:
yes, concurrent vehicle

Results and discussion

Results: P0 (first parental animals)

General toxicity (P0)

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
hypersalivation in all groups
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
reduced weight gain and food consumption in the mid- and high-level dose groups (F)
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
reduced weight gain and food consumption in the mid- and high-level dose groups (F)
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
dark coloured livers in high dosed males
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
thickening of the urinary bladder epithelium in high dosed males
Other effects:
not examined

Reproductive function / performance (P0)

Reproductive function: estrous cycle:
not specified
Reproductive function: sperm measures:
not examined
Reproductive performance:
no effects observed

Details on results (P0)

Blood chemistry analyses demonstrated increased levels of blood urea nitrogen, serum aspartate aminotransferase and chloride in both sexes of the two highest groups and increased serum alanin aminoteransferase levels in the high dose males.
Two of the high-dose female rats showed signs of difficult labor; all their offspring died by day 3 of lactation.

Effect levels (P0)

Dose descriptor:
NOAEL
Effect level:
120 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female

Results: F1 generation

General toxicity (F1)

Clinical signs:
no effects observed
Mortality / viability:
mortality observed, treatment-related
Description (incidence and severity):
decrease in survival rate
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
decrease in body weight.
Sexual maturation:
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
no effects observed
Histopathological findings:
not specified

Effect levels (F1)

Dose descriptor:
NOAEL
Generation:
F1
Effect level:
300 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female

Overall reproductive toxicity

Reproductive effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Parental toxicity was observed at 300 and 750 mg/kg/day based on clinical observations, weight gain and food consumption, and clinical chemistry.
Litter toxicity was observed at 750 mg/kg/day based on litter size and body weight, considered to be secondary to parental toxicity.
Executive summary:

A repeated dose toxicity and reproductive/developmental toxicity screening test on para-toluenesulfonamide (metabolite from Chloramine T) was performed according to OECD TG 422. Rats were treated by gavage with 0, 120, 300 or 750 mg/kg bw, males for 42 days before mating and females for 14 days before mating up to day 3 of lactation. Dams and litters were examined on post-natal day 4. A dose-related hypersalivation was observed in all treatment groups. Weight gain and food consumption were reduced in the mid- and high-level dose groups (F). Blood chemistry revealed increased levels of blood urea nitrogen, serum aspartate aminotransferase, and chloride in both sexes in the two highest dose groups. Increased serum alanine aminotransferase was observed at 750 mg/kg bw. In the males of the highest dose group dark coloured livers were seen at gross pathology and thickening of the urinary bladder epithelium at histopathological examination. Reduced weight gain and food consumption was observed in the highest 2 dose groups.

The test compound affected neither mating performance nor fertility. In the high-dose group, newborns showed a significant decrease in body weight and survival rate. Two of the high-dose female rats showed signs of difficult labor; all their offspring died by d 3 of lactation. Morphological observations for offspring revealed no teratogenic effect of the test substance. NOAEL for parental toxicity was 120 mg/kg/day; NOAEL for F1 generation was 300 mg/kg. The estimated dose of low concern for reproduction was calculated as 0.6 mg/kg/day.