Registration Dossier

Diss Factsheets

Toxicological information

Repeated dose toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
04-1975 and 01-1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
non-GLP conform

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1975
Report date:
1976

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
tert-butyl peracetate
EC Number:
203-514-5
EC Name:
tert-butyl peracetate
Cas Number:
107-71-1
Molecular formula:
C6H12O3
IUPAC Name:
tert-butyl peracetate
Details on test material:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: in the refrigeratore in the dark between +10 and +30°C

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands
- Weight at study initiation: average bw 67 g
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: glass exposure cylinder with stainless steel interior
- Method of holding animals in test chamber: each exposure cylinder accommodated five male and five female rats, seperated from one another
- Temperature: 23°C
- Air flow rate: 10 L/min

TEST ATMOSPHERE
- Brief description of analytical method used: TBPA was evaporated by passing a measured, filtered and dried air flow through glass evaporation columns, packed with chromosorb W (60 to 80 mesh) at 23°C.
- Samples taken from breathing zone: yes

Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Samples of the air were taken at intervals and analysed by means of GLC, using a 0.35 m x 4 mm column of stainless steel tubing packed with QF-1 4.8% / diglycerol 0.13% on Chrom G-AW-DHCS and a flame ionization detector.
Duration of treatment / exposure:
28 days
Frequency of treatment:
7 hours/day, 5 days/week fo a four-week period
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0, 2, 11, 52 ppm
Basis:
other: active ingredient
Remarks:
Doses / Concentrations:
0, 10.9, 60.4, 285.6 mg/m3
Basis:
other: active ingredient
No. of animals per sex per dose:
10
Control animals:
yes, concurrent vehicle
Positive control:
no positive control

Examinations

Observations and examinations performed and frequency:
BODY WEIGHT: Yes
- Time schedule for examinations: Individual body weights were recorded weekly.
- How many animals: 10 male and 10 female rats per doses

HAEMATOLOGY: Yes
Haematological data (haemoglobin content, haematocrit value, and erythrocyte and leucocyte counts) were collected in week 4.
- How many animals: 10 male and 10 female rats per doses

URINALYSIS: Yes
- Urine examinations were made, including appearance, pH, glucose, protein, occult blood, ketones, using test stripes, and microscopy of the sediment in pooled urine samples of each group.
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
- The organ weight of the heart, kidneys, liver, spleen and lung was determined of groups of ten male and ten female rats after a test period of four weeks.
HISTOPATHOLOGY: Yes
- Tissue samples of the organs described before and of the head (after removal of the skin, brain and lower jaw) were taken.
Other examinations:
No other examinations
Statistics:
Student's t-test

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Growth of the males of the low and intermediate doses groups was slightly, but statistically significantly retarded during the first weeks (see table 1 other information on results)
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
slightly elevated lung weight in males and a slightly lowered spleen weight in females at the low exposure levele; see table 2 (other information on results)
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not examined
Details on results:
GROSS PATHOLOGY: Infrequently occuring gross changes unrelated to the inhalation of the active ingredient included pale livers and kidneys, a striking lobular pattern of the liver surface and hydronephrosis.

HISTOPATHOLOGY: NON-NEOPLASTIC: Histopathological changes occurred to about the same degree and frequency in the various groups studied histologically and are, moreover, quite common findings in the strain of rats used.


Effect levels

open allclose all
Key result
Dose descriptor:
NOAEC
Effect level:
52 ppm
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed up to 52 ppm.
Dose descriptor:
NOAEC
Effect level:
0.28 mg/L air
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed
Dose descriptor:
NOAEC
Effect level:
104 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed.
Dose descriptor:
NOAEC
Effect level:
0.56 mg/L air
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No adverse effects observed.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Table 1: Mean body weights of groups of ten male and ten female rats

Animal

TBP [ppm]

Mean body weight at end of week

        0                      1                         2       3                    4

Males

1

0

67

124

147

188

221

2

2

66

111***

134***

173**

193*

3

11

67

111***

134***

176*

208

4

52

67

121

145

186

215

Females

1

0

66

105

117

136

149

2

2

67

103

117

138

152

3

11

67

106

118

142

158

4

52

67

106

119

136

149

*p < 0.05, **p < 0.01, ***p < 0.001

Table 2: Relative organ weights (in g/100 g body weight) and their standard deviations of groups of ten male and ten female rats after test period of four weeks

TBP [ppm]

heart

kidneys

liver

spleen

lung

Males

0

0.383 (0.015)

0.80 (0.02)

5.47 (0.20)

0.293 (0.009)

0.61 (0.02)

2

0.417 (0.029)

0.85 (0.06)

5.67 (0.45)

0.303 (0.022)

0.69* (0.04)

11

0.378 (0.011)

0.79 (0.01)

5.26 (0.12)

0.271 (0.012)

0.58 (0.01)

52

0.377 (0.013)

0.77 (0.01)

5.38 (0.11)

0.290 (0.007)

0.63 (0.03)

Females

0

0.397 (0.013)

0.80 (0.02)

4.62 (0.13)

0.300 (0.012)

0.66 (0.03)

2

0.393 (0.014)

0.79 (0.01)

4.76 (0.08)

0.269* (0.008)

0.65 (0.01)

11

0.405 (0.008)

0.78 (0.02)

4.71 (0.07)

0.297 (0.018)

0.64 (0.01)

52

0.386 (0.008)

0.79 (0.01)

4.48 (0.14)

0.288 (0.009)

0.65 (0.02)

*p < 0.05, according to Student's t-test

Applicant's summary and conclusion

Conclusions:
The results of the present four-week inhalation study indicates that the NOAEC of the active ingredient is higher than 52 ppm (correspond to 0.28 mg/L). Hence, the NOAEC for the test material (50% act. ingr. in Shellsol T) is expected to be approx. 0.56 mg/L.
Executive summary:

The sub-acute inhalation toxicity of the test substance (50% active ingredient) was studied in rats by exposing them 7 hours/day, 5 days/week to atmosphere, containing the vapour of the active ingredient at the concentrations 0, 2, 11 and 52 ppm (~ 0.28 mg/L), for a four-week period. Observations were made of behaviour, general appearance, growth, haematology, urine composition, organ weights and gross as well as microscopic pathology. None of the criteria applied revealed treatment-related effects. From the results of the present four-week inhalation study with the test substance it appeared that no deleterious effects could be demonstrated in rats exposed repeatedly to concentrations of the active ingredient of up to 52 ppm (0.28 mg/L) during twenty exposure days. It is concluded, therefore, that the NOAEC is higher than 0.28 mg/L. Therefore, the NOAEC for the test material (50% act. ingr. in Shellsol T) is expected to be approx. 0.56 mg/L.