2,2-bis(hydroxymethyl)butanoic acid

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral, other

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1995

Report date:

1995

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Japanese Guidelines on Industrial Chemicals (1986), equivalent to 92/69/EEC used.

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

no

Test material

Test material information

1

Reference substance name:

2,2-bis(hydroxymethyl)butanoic acid

EC Number:

424-090-1

EC Name:

2,2-bis(hydroxymethyl)butanoic acid

Cas Number:

10097-02-6

Molecular formula:

C6H12O4

IUPAC Name:

2,2-bis(hydroxymethyl)butanoic acid

Details on test material:

supplier: study sponsor
Batch No: 4K02

Test animals

Species:

rat

Strain:

other: SD (Crj:CD)

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: purified water

Details on oral exposure:

The four week treatment period was followed by a 2-week recovery period (groups 1,4 and 5 only, 6 males and 5 females per group).

Duration of treatment / exposure:

28 days

Frequency of treatment:

Dosing regime: 7 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

8 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

40 mg/kg bw/day (nominal)

Doses / concentrations 4

Dose / conc.:

200 mg/kg bw/day (nominal)

Doses / concentrations 5

Dose / conc.:

1 000 spores/kg bw/day (nominal)

No. of animals per sex per dose:

Male: 6 animals at 0 mg/kg bw/day
Male: 6 animals at 8 mg/kg bw/day
Male: 6 animals at 40 mg/kg bw/day
Male: 6 animals at 200 mg/kg bw/day
Male: 6 animals at 1000 mg/kg bw/day
Female: 6 animals at 0 mg/kg bw/day
Female: 6 animals at 8 mg/kg bw/day
Female: 6 animals at 40 mg/kg bw/day
Female: 6 animals at 200 mg/kg bw/day
Female: 6 animals at 1000 mg/kg bw/day

Results and discussion

Results of examinations

Details on results:

Clinical observations:
There were no deaths.
Soiled perineal region was observed in male rats treated at 1000 mg/kg/day. Four males showed soiling from 19 days after commencement of treatment until the end of the treatment period and one showed only transient soiling. No such effects were seen in any animal during the recovery period.
No clinical signs were noted in any other group.

Laboratory findings:
No treatment-related changes in urinalysis, blood chemistry or haematology parameters were found.

Effects in organs:
No treatment-related effects were observed.

Effect levels

1

Key result

Dose descriptor:

NOAEL

Effect level:

1 000 mg/kg bw/day (nominal)

Sex:

male/female

Remarks on result:

other: original NCD unit is mg/kg/day.

2

Key result

Dose descriptor:

NOEL

Effect level:

200 mg/kg bw/day (nominal)

Sex:

male/female

Remarks on result:

other: original NCD unit is mg/kg/day.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No specific toxic effect was observed

Executive summary:

To evaluate the toxicity of the test substance a subacute study in rats by oral route was performed. The study was conducted in accordance with B.7 92/69/EEC of July 31, 1992. The test substance was administered orally via gavage to groups of 6 male and 6 female Crj:CD (SD) IGS rats using target doses of 0, 8, 40, 200 and 1000 mg/kg bw/d for 4 weeks. Based oh the results of the study, 1000 mg/kg bw/d was established as the no-observed-adverse-effect-level (NOAEL) and 200 mg/kg bw/d the no-observed-effect-level (NOEL) for male and female rats.