tert-butyl peracetate

Repeated dose toxicity: inhalation

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

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)

Deviations:

yes

Remarks:

no details on animal husbandry, exposure 7 h/day instead of 6 h/day, no food consumption measured, lesser haematological parameters measured, no clinical chemistry, lesser organ weights determined, lesser histopathological determinations

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

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 ethaneperoxoate

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 for a four-week period

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

0 ppm

Remarks:

control

Doses / concentrations 2

Dose / conc.:

2 ppm

Remarks:

equals 10.9 mg/m3

Doses / concentrations 3

Dose / conc.:

11 ppm

Remarks:

equals 60.4 mg/m3

Doses / concentrations 4

Dose / conc.:

52 ppm

Remarks:

equals 285.6 mg/m3

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

Endocrine findings:

not specified

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, non-treatment-related

Description (incidence and severity):

Statistically significant differences in relative organ weight did not occur between the groups, apart from a slightly elevated lung weight in males and a slightly lowered spleen weight in females at the low exposure level. These deviations are not considered of any toxicological importance, because the relative weights of these organs at the higher dose levels did not differ significantly from those of the controls.

Gross pathological findings:

effects observed, non-treatment-related

Description (incidence and severity):

Upon gross examination the lungs of both the test and control animals looked normal and there was no evidence of treatment-related changes in any of the other organs. Infrequently occurring gross changes unrelated to the inhalation included pale livers and kidneys, a striking lobular pattern of the liver surface and hydronephrosis.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, non-treatment-related

Description (incidence and severity):

Neither the respiratory tract nor any of the other organs examined showed lesions that could be associated with the exposure. All 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.

Histopathological findings: neoplastic:

not examined

Other effects:

no effects observed

Effect levels

1

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.

2

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

3

Dose descriptor:

NOAEC

Effect level:

104 ppm

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse effects observed.

4

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

Key result

Critical effects observed:

no

Any other information on results incl. tables

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

Animal	TBPA [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

TBPA [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.