Chloramide

Toxicity to reproduction

Administrative data

Endpoint:

toxicity to reproduction

Remarks:

other: reproductive study

Type of information:

experimental study

Adequacy of study:

key study

Study period:

no data

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study with acceptable restrictions.

Data source

Reference

Reference Type:

publication

Title:

Reproductive effects of alternative disinfectants

Author:

Carlton B.D., Barlett P., Basaran A., Kate Colling K., Osis I., and Smith M.K.

Year:

1986

Bibliographic source:

Environmental Health Perspective, Vol. 69, pp. 237-241, 1986.

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study reported here was designed to evaluate reproductive effects in rats. Males were treated for 56 days and females for 14 days prior to breeding and throughout the 10-day breeding period. Females were treated throughout gestation and lactation. Following breeding, the males were necropsied and evaluated for sperm parameters and reproductive tract histopathology. Adult females and some pups were necropsied at weaning on postnatal day 21. Other pups were treated postweaning until 28 or 40 days of age. These pups were evaluated for the day of vaginal potency and thyroid hormone levels.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Chloramide

EC Number:

234-217-9

EC Name:

Chloramide

Cas Number:

10599-90-3

Molecular formula:

ClH2N

IUPAC Name:

chloranamine

Test material form:

other: in solution

Details on test material:

Chloramine stock solution was prepared by titrating chlorine stock solution with ammonia.

Test animals

Species:

rat

Strain:

Long-Evans

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI)
- Age at study initiation: 4-6 weeks
- Housing: 2 per cage in polycarbonate cages
- Diet : Purina Certified Roden Chow 5002, ad libitum.
- Water : deionized water, ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 69-75°F
- Humidity (%): 40-60
- Photoperiod : 12 hrs dark/12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Twelve males rats per dose group were gavaged with 0, 2.5, 5.0 or 10.0 mg/kg for 56 days prior to breeding and trhoughout the 10-day breeding period. Twenty -four female rats per dose group were given the same dose levels of monochloramine by gavage 14 days prior to breeding and throughout breeding, gestation, and lactation until the pups were weaned on day 21.

Details on mating procedure:

- M/F ratio per cage: 1/2
- Length of cohabitation:10-day breeding
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): individually

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Males were exposed to chloramine for 56 days prior to breeding and throughout the 10-day breeding period.
Females were exposed for 14 days prior to breeding and throughout breeding, gestation and lactation until the pups were weaned on day 21.

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 2.5, 5.0, or 10 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

12 male rats per dose
24 female rats per dose

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Doses chosen were the highest practicable considering solution stability and potential gastric irritation.

Positive control:

No

Examinations

Parental animals: Observations and examinations:

CAGE SIDE OBSERVATIONS: No

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes

Oestrous cyclicity (parental animals):

No data

Sperm parameters (parental animals):

Parameters examined in male parental generations:
sperm count in epididymides, sperm motility, sperm morphology

Litter observations:

Litters were evaluated for viability, litter size, day of eye opening, body weight gain, and gross external abnormalities. The day on which all pups in a litter had both eyes open was designated as the day of eye opening. At necropsy on lactation day 21, 10 pups/sex/dose were bled for complete blood counts and hormone

Postmortem examinations (parental animals):

SACRIFICE
- Male animals: Following the breeding period.
- Maternal animals: On lactation day 21.

GROSS NECROPSY
- Gross necropsy consisted of reproductive tract examinations.

HISTOPATHOLOGY / ORGAN WEIGHTS
Male: The reproductive tract, including testis, epididymis, prostate, and seminal vesicles, was removed weighed, and, except for the right cauda epididymis, preserved in neutral buffered formalin for histopathologic evaluation
Female: The reproductive tract was removed, weighed, and preserved for histopahtologic evaluation.

Postmortem examinations (offspring):

SACRIFICE
- The F1 offspring were sacrificed on lactation day 21.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows:

GROSS NECROPSY
- Gross necropsy consisted of reproductive tract examinations.

HISTOPATHOLOGY / ORGAN WEIGTHS
Not performed.

Statistics:

no statistics were performed.

Reproductive indices:

Not evaluated.

Offspring viability indices:

Not evaluated.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Dermal irritation (if dermal study):

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

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

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Details on results (P0)

No clinical signs of toxicity, hematology changes, or evidence of body weight suppression were observed for adult male or female rats dosed with 0, 2.5, 5.0, or 10.0 mg/kg NH2Cl by gavage for up to 72 days. Fertility, fecundity, lenght of gestation, litter size, and litter survival rates were unchanged by NH2Cl treatment. No treatment-related adverse reproductive effects were observed in adult male rats treated with up to 10.0 mg/kg NH2Cl. The sperm concentration ranged from 587.5 x 10exp6 sperm/g epididymal tissue to 644 x 10 exp6 sperm/g epididymal tissue. the percentage of abnormal sperm morphology ranged from 0.4 +/- 0.5 % to 2.6+/- 4.7 %, but did not varied in a dose-dependent manner. Sperm motility and sperm progressive movement were unaffected by dose exposure. No treatment-related histopathologic lesions were observed in the reproductive tracts of male or female rats.

Effect levels (P0)

Dose descriptor:

NOAEL

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

haematology

Results: F1 generation

General toxicity (F1)

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Body weight and weight changes:

no effects observed

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings:

not examined

Details on results (F1)

Litter size and litter survival rates were unchanged by NH2Cl treatment. Mean pup weight was unaltered. the average day of opening and the average day of observed vaginal patency (day 31.8 to day 32.6) were comparable among groups.

Effect levels (F1)

Dose descriptor:

NOAEL

Effect level:

10 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No adverse reproductive effects following subchronic administration of chloramine were observed in this study.

Executive summary:

The reproductive effects of chloramine administered by gavage in Long-Evans rats were examined. Males were treated for 56 days and females for 14 days prior to breeding and throughout the 10 -day breeding period. Females were treated throughout gestation and lactation. Following breeding, the males were necropsied and evaluated for sperm parameters and reproductive tract histopathology. adult females and some pups were necropsied at weaning on postnatal day 21. Other pups were treated postweaning until 28 or 40 days of age. These pups were evaluated for the day of vaginal patency and thyroid hormone levels. No differences were observed between control rats and those rats exposed to 10 mg/kg/day chloramine when fertility, viability, litte size, day of eye opening, or day of vaginal patency were evaluated. No alterations in sperm count, sperm direct progressive movement (µm/sec), percent motility, or sperm morphology were observed among adult male rats. In addition, male and female reproductive organ weights were comparable to their respective controls groups, and no significant histopathologic changes were observed among chloramine -treated male and female rats.