Chlorine

Toxicity to reproduction

Administrative data

Endpoint:

one-generation reproductive toxicity

Remarks:

based on test guideline (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: No deficiencies.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]

Deviations:

yes

Remarks:

dose administration to males only 8 weeks instead of 10 as recommended by the guideline

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hypochlorous acid

EC Number:

232-232-5

EC Name:

Hypochlorous acid

Cas Number:

7790-92-3

IUPAC Name:

hypochlorous acid

Details on test material:

Aqueous chlorine (HOCl)

Test animals

Species:

rat

Strain:

Long-Evans

Sex:

male/female

Details on test animals or test system and environmental conditions:

Source: Charles River Breeding Laboratories, Portage, USA 4-6 weeks old, weight not stated

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

Total volume applied: 10 mL/kg

Details on mating procedure:

One male housed with two females throughout breeding period. Duration of mating: 10 days

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Duration of exposure before mating Males: 56 days; Females: 14 days Duration of exposure in general P, F1 Males: 56 days prior to breeding and throughout the 10-day breeding period.Females: 14 days prior to breeding and throughout breeding, gestation and lactation until pups were weaned on day 21.

Frequency of treatment:

daily

Details on study schedule:

Male were dosed 56 days prior and throughout breeding, females were dosed 14 days prior to breeding, throughout breeding, gestation and lactation until day 21 of lactation.

Doses / concentrations

Remarks:

Doses / Concentrations:1, 2, or 5 mg/kg bw/day Basis:nominal conc.

No. of animals per sex per dose:

12 males, 24 females

Control animals:

yes, concurrent vehicle

Examinations

Parental animals: Observations and examinations:

Clinical signs Yes Body weight Yes

Oestrous cyclicity (parental animals):

Not stated

Sperm parameters (parental animals):

Testis weight Epididymides weight Sperm motility Sperm morphology Sperm concentration in epididymides

Litter observations:

Number of pups Stillbirths Litter size Live births Presence of gross anomalies Weight gain Weight of reproductive organs Day of eye opening Complete blood countsHormone analysis Vaginal patency

Postmortem examinations (parental animals):

Organ weights P and F1: Female reproductive tract Testes Epididymides (total and cauda) ProstateSeminal vesicles Histopathology P and F1 Organs of the reproductive tract

Postmortem examinations (offspring):

Organ weights P and F1:Female reproductive tract Testes Epididymides (total and cauda) ProstateSeminal vesicles Histopathology P and F1 Organs of the reproductive tract

Statistics:

not stated

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:

no effects observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Other effects:

not examined

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:

not examined

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Effect levels (P0)

1

Key result

Dose descriptor:

LOAEL

Effect level:

> 5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

reproductive function (sperm measures)

reproductive performance

Remarks on result:

not determinable due to absence of adverse toxic effects

2

Key result

Dose descriptor:

NOAEL

Effect level:

>= 5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

clinical signs

mortality

body weight and weight gain

organ weights and organ / body weight ratios

gross pathology

histopathology: non-neoplastic

reproductive function (sperm measures)

reproductive performance

Remarks on result:

not determinable due to absence of adverse toxic effects

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:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings:

no effects observed

Effect levels (F1)

1

Key result

Dose descriptor:

LOAEL

Generation:

F1

Effect level:

> 5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

sexual maturation

clinical signs

mortality

body weight and weight gain

gross pathology

histopathology: non-neoplastic

histopathology: neoplastic

other: thyroid hormone levels

Remarks on result:

not determinable due to absence of adverse toxic effects

2

Key result

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

>= 5 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

sexual maturation

clinical signs

mortality

body weight and weight gain

gross pathology

histopathology: non-neoplastic

histopathology: neoplastic

other: thyroid hormone levels

Remarks on result:

not determinable due to absence of adverse toxic effects

Overall reproductive toxicity

Reproductive effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

LO(A)ELParent males> 5.0 mg/kg bw/dayParent females> 5.0 mg/kg bw/dayF1 males> 5.0 mg/kg bw/dayF1 females> 5.0 mg/kg bw/dayNO(A)ELParent males≥ 5.0 mg/kg bw/dayParent females≥ 5.0 mg/kg bw/dayF1 males≥ 5.0 mg/kg bw/dayF1 females≥ 5.0 mg/kg bw/day

Executive summary:

No differences were observed between control rats and those rats exposed to up to 5 mg/kg bw/day of the test material when fertility, viability, litter size, day of eye opening or day of vaginal patency were evaluated. No alterations in sperm count, sperm direct progressive movement, percent motility or sperm morphology were observed among adult male rats. In addition, male and female reproductive organ weights were comparable to the control groups and no significant histopathological changes were observed among treated male female rats.