Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-11-12 to 1996-11-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study conducted with minor deviations: temperature in the experimental room was outside the target range
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
yes
Remarks:
temperature in the experimental room was outside the target range
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
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
Test material form:
other: solid
Details on test material:
- Name of test material (as cited in study report): DMBA
- Physical state: White solid
- Analytical purity: 99 % by weight
- Lot/batch No.: 5J01
- Date of receipt: 1996-10-09
- Expiration date of the lot/batch: April 1997 (Assumed to be stable for 6 months from date of receipt at Huntingdon Life Sciences)
- Storage condition of test material: Room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd, Bicester, Oxon, England.
- Age at study initiation: Approximately 4-7 weeks
- Weight at study initiation: 75-89 g
- Fasting period during the study: Animals were fasted for overnight period before test item administration and for approximately 4 h after dosing.
- Housing: Animals were housed in groups of 5/sex in metal cages with wire mesh floors
- Diet: Standard laboratory rodent diet (SDS R&M 1), ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 17-19.5 °C
- Humidity: 39-59 %
- Air changes: 10-15 air changes/hour
- Photoperiod: 12 h dark / 12 h light

IN-LIFE DATES: From: 1996-11-12 To: 1996-11-26

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 % w/v

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION: DMBA was formulated on the day of dosing at a concentration of 20 % w/v in distilled water.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Cages of rats were checked at least twice daily for any mortalities. Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only).
- Frequency of weighing: Bodyweight of each rat was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: Yes; all animals were killed on Day 15 by cervical dislocation and were subjected to a macroscopic examination.
Statistics:
None

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality was observed.
Mortality:
No mortality was observed.
Clinical signs:
- Piloerection was observed in all rats within five minutes of dosing; later on Day 1 it was accompanied by hunched posture in all animals and soft to liquid faeces in all males and three females. In addition, one female showed increased salivation within 5 minutes of dosing which had resolved after one hour.
- All signs of reaction, with the exception of piloerection, had resolved within 24 h of dosing. There were no other signs of reactions `to treatment and recovery, as judged by external appearance, was complete and behaviour was normal in all animals by Day 8.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were observed at the study termination necropsy.
Other findings:
None

Any other information on results incl. tables

None

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test conditions, the oral LD50 for DMBA is higher than 2000 mg/kg bw in rats therefore it is not classified according to the Annex VI to the Directive 67/548/EEC and the CLP Regulation (EC) N° (1272-2008).
Executive summary:

Test Guidance

Performed according to EU Method B.1 (Acute Toxicity (Oral)) guideline and in compliance with GLP,

Method

Groups (5/sex/dose) of CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley(CD)) were given a single oral (gavage) dose of DMBA at 2000 mg/kg bw. Animals were then observed for mortality, clinical signs and bodyweights for 14 days.

Results

No mortality was observed. Clinical signs of reaction to treatment comprised piloerection, hunched posture (in all animals), soft to liquid faeces (in all males and three females) and increased salivation (in one female). There were no other signs of reaction to treatment and recovery was complete in all rats by Day 8. All animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were observed at the study termination necropsy. In this study, the combined oral LD50 of DMBA was considered to be higher than 2000 mg/kg bw in rats.

Conclusion

Under the test conditions, the oral LD50 for DMBA is higher than 2000 mg/kg bw in rats therefore it is not classified according to the CLP Regulation (EC) N° (1272-2008).

Categories Display