Methanesulphonic acid

Developmental toxicity / teratogenicity

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:

other: GLP Guideline study with acceptable restrictions (Not exposed until day prior to scheduled kill, no toxic effects of highest dose applied)

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Reference 2

Reference Type:

publication

Title:

HPVIS, IUCLID Data Set for Methanesulphonic acid, CAS no. 75-75-2

Author:

US-EPA

Year:

2003

Bibliographic source:

HPV Chemicals Challenge Program OPPT NCIC 201-14249B

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 414 (Prenatal Developmental Toxicity Study)

Deviations:

yes

Remarks:

Not exposed until day prior to scheduled kill, no toxic effects of highest dose applied

GLP compliance:

yes

Remarks:

Wil Research Laboratories

Test material

Test material information

Constituent 1

Reference substance name:

Methanesulphonic acid

EC Number:

200-898-6

EC Name:

Methanesulphonic acid

Cas Number:

75-75-2

Molecular formula:

CH4O3S

IUPAC Name:

methanesulfonic acid

Details on test material:

- Name of test material (as cited in study report): Methanesulfonic acid
- Physical state: clear colorless liquid
- Composition of test material, percentage of components: 70.15 % in water
- Lot/batch No.: C06G
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, Michigan)
- Age at study initiation: approx. 81 days
- Weight at study initiation: 266±9.5 g
- Housing: single
- Diet (e.g. ad libitum): Certified Rodent Labdiet, PMI Feeds Inc.
- Water (e.g. ad libitum): drinking water
- Acclimation period: 11 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): ca. 22
- Humidity (%): 44.5-61.2
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

VEHICLE
- Vehicle: deionized water
- Concentration in vehicle: 25, 25 and 50 mg/ml for the 25, 100 and 400 mg/kg bw/day groups, respectively
- Amount of vehicle (if gavage): 1, 4 and 8 ml/kg bw for the 25, 100 and 400 mg/kg bw/day groups, respectively

Analytical verification of doses or concentrations:

yes

Details on mating procedure:

- Impregnation procedure: cohoused (paired in the home cage of the male for mating)
- If cohoused:
- M/F ratio per cage: paired (1/1)
- Proof of pregnancy: sperm in vaginal smear day 0 of pregnancy

Duration of treatment / exposure:

GD 6 to 15

Frequency of treatment:

once daily

Duration of test:

up to GD 20

Doses / concentrations

Remarks:

Doses / Concentrations:
25, 100 and 400 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

25 females

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: Based on dose range-finding developmental toxicity study on Methane Sulfonic Acid (MSA) in rats. MSA was orally administered to 5 groups of 8 rats once daily for GD 6-15 at dosage levels of 25, 50, 100, 200 and 300 mg/kg bw/day. No mortalities were observed. All maternal animals survived to the scheduled necropsy on GD 20. Rales, laboured respiration and gasping; findings of red material around the nose and/or mouth in the 100, 200, and 300 mg/kg bw/day groups. Slight mean body weight losses (2 to 5 g) and reduction in food consumption occured in the 100, 200 and 300 mg/kg bw/day groups during gestation days 6 to 9 when evaluated on a group mean basis. Mean body weights, gravid uterine weights, net body weights and net body weight gains were unaffected by the treatment at all dose levels. No treatment-related internal findings were observed at necropsy at any dose level. No effects were observed at any dose level on intrauterine growth and survival. No external developmental variations or malformations were observed in any of the fetuses in the treated groups.

Examinations

Maternal examinations:

CLINICAL OBSERVATIONS: Yes
- Time schedule: twice a day, from day 0 through day 20

BODY WEIGHT: Yes
- Time schedule for examinations: on day 0, daily on day 6 to 16, and on day 20. Mean body weight changes were calculated for each corresponding interval and also for days 6-9, 9-12, 12-16, 6-16 and 0-20.

FOOD CONSUMPTION: Yes
- Time schedule: on day 0, daily on day 6 to 16, and on day 20

POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 20
- Organs examined: Laparohysterectomy: uteri and ovaries, numbers of fetuses, early and late resorptions, total implantations and corpora lutea; mean gravid uterine weights and net body weight changes were calculated for each group; fetuses were weighed, sexed and examined for external, visceral and skeletal malformations and developmental variations.

Ovaries and uterine content:

The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: number of fetuses

Fetal examinations:

- External examinations: Yes: [all per litter]
- Soft tissue examinations: Yes: [all per litter]
- Skeletal examinations: Yes: [all per litter]
- Head examinations: No data

Statistics:

Chi-square test for fetal sex ratios; Fisher's Exact test for malformations and variations; Mann-whitney u-test for early and later resorptions, dead fetuses, postimplantation losses; One-way Anova with dunnett's test for maternal examinations and Kruskal-Wallis test for litter proportions of intrauterine data.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
Clinical observations: No clinical signs that could be attributed to the test substance were observed in the treated groups. No mortality was observed until day 20 (necropsy). Body weight and food consumption were not affected by the treatment.
Necropsy: No treatment related internal findings were observed at any dose level. Intrauterine growth and survival were unaffected by test substance administration at all dose levels.

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

>= 400 mg/kg bw/day

Basis for effect level:

other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Fetal external, soft tissue and skeletal malformations were observed in 0(0), 2(2), 2(2) and 1(1) fetuses (litters) in the control, 25, 100, and 400 mg/kg bw/day groups, respectively, and were considered to be spontaneous in origin. The developmental variations observed in the treated groups occurred similarly in the control group and/or in a manner which was not dose-related.

Effect levels (fetuses)

Dose descriptor:

NOAEL

Effect level:

>= 400 mg/kg bw/day

Basis for effect level:

other: teratogenicity

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified