Dibromomethane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Data source

Reference

Reference Type:

publication

Title:

Results of a short -term toxicity study for three organic chemicals found in Niaga ra river drinking water

Author:

Komsta, E., I. Chi, V.E. Valli et al.

Year:

1988

Bibliographic source:

Bull. Environ. Contam. Toxicol. 41:515 − 522.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

not specified

Test material

Test material information

1

Reference substance name:

Dibromomethane

EC Number:

200-824-2

EC Name:

Dibromomethane

Cas Number:

74-95-3

Molecular formula:

CH2Br2

IUPAC Name:

dibromomethane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: drinking water

Vehicle:

other: hemulfor as emulsifier

Duration of treatment / exposure:

28 days

Doses / concentrations

Remarks:

0.1,1.2,11.9,124 mg/kg/day males
0.1,0.9,8.6 and 90 mg/kg/day females
(based on group water consumption and average body weight)

No. of animals per sex per dose:

10 male and 10 females

Control animals:

yes

Results and discussion

Results of examinations

Details on results:

Endpoints evaluated at termination of exposure included hematology, serum chemistry, andhepatic microsomal enzymeactivity (aniline hydroxylase, aminopyrine demethylase, and ethoxyresorufin deethylase). The hematology determinations consisted ofhemoglobin, packed cell volume, erythrocyte count,
total and differential leukocyte counts, and platelet counts. The serum chemistry determinations consisted of sodium, potassium, calcium, inorganic phosphate,
total bilirubin, total protein, cholesterol, glucose, uric acid, alkaline phosphatase, aspartate aminotransferase, and lactate dehydrogenase.
Gross necropsy and selected organ weight measurements (brain, heart, liver, spleen, and kidneys) were performed on all animals at termination of exposure. Comprehensive histological examinations (29 tissues, including male
and female reproductive tissues) were conducted but limited tothe control and high-dose groups.
The investigators used data from the water control group as baseline values for evaluation purposes because a comparison of data from the water and vehicle control groups showed that there were no significant differencesbetween the groups .

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

8.6 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

other: decrease inserum lactate dehydrogenase

2

Dose descriptor:

LOAEL

Effect level:

124 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: histological changes

3

Dose descriptor:

LOAEL

Effect level:

90 mg/kg bw/day (nominal)

Sex:

female

Basis for effect level:

other: decrease inserum lactate dehydrogenase

4

Dose descriptor:

NOAEL

Effect level:

11.9 mg/kg bw/day (nominal)

Sex:

male

Basis for effect level:

other: histological changes

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The investigators used data from the water control group as baseline values for evaluation purposes because a comparison of data from the water and vehicle control groups showed that there were no significant differences between the groups .

The only effects attributable to methylene bromide exposure were reduced serum lactate dehydrogenase activity in females at ≥8.6 mg/kg-day and histological alterations in the liver and thyroid in males at 124 mg/kg-day. Serum lactate dehydrogenase activity in the 0.1, 0.9, 8.6, and 90 mg/kg-day

females was 21.6, 17.2, 27.4, and 31.2% lower than water controls,respectively. Although statistically significant (p≤0.05) at ≥8.6 mg/kg-day, the investigators did not consider the decreases in serum lactate dehydrogenase to be biologically significant or related to any histological changes. Given the lack of a basis for toxicological concern of a decrease inserum lactate dehydrogenase (as opposed to an increase), the effect is discounted for determination of a

LOAEL. In males, the histological changes in the liver were characterized as

minimal-to-mild increases in perivenouscytoplasmic homogeneity and periportal cytoplasmic density; the incidence in the 124 mg/kg-day group was 8/10 compared to 3/10 in water controls and 5/10 in vehicle controls. The histological changes in the thyroid of the 124 mg/kg-day males were also

minimal-to-mild in severity and included increased epithelial height (8/10 compared to 1/10 in water controlsand 4/10 in vehicle controls) and reduced colloid density (2/10 compared to 0/10 in water controls and 0/10 in vehicle controls). Other histological findings included low incidences of minimal-

to-mild renal tubular cytoplasmic inclusions in males at 124 mg/kg-day

(4/10 compared to 2/10 in water controls and 1/10 in vehicle controls) and females at 90 mg/kg-day (3/10 compared to 0/10 in water controls and 0/10 in vehicle controls). Histology examinations were not performed in any tissues at lower doses in either sex. Although these effects were generallymild and not accompanied by overt functional changes, they are indicative

of compound-related changes that could progress to more severe outcomes. Consequently, the highest doses tested in females (90 mg/kg-day) and males (124mg/kg-day) are considered to be LOAELs. NOAELs of 8.6 mg/kg-day in females and 11.9 mg/kg-day in males are established in this study