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Description of key information

Based on the test material containing 50% of the active ingredient the following values are expected to be 3843 mg/kg bw (combined male/female rats) for the acute oral LD50 value, 9.2 mg/L (as vapour and aerosol) for the acute inhalation LC50 value as wells as 7135.5 mg/kg bw (combined male/female rats) for the acute dermal LD50 value. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978-08-23 and 1978-12-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Industries, Inc., Indianapolis, Indiana
- Weight at study initiation: 222 to 300 g
- Fasting period before study: for an overnight period of approximately 18 hours immediately preceding oral administration during which food, but not water, was withheld
- Housing: housed by sex, in groups of five rats per cage, in hanging wire-mesh cages in temperature and humidity controlled quarters.
- Diet and water: e.g. ad libitum
- Acclimation period: 27 days


Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
All the dosage levels were administered at a volume of 10 mL/kg.
Doses:
807.1, 1281, 2034, 3229 and 5126 mg/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Mortality was observed, only, during the first 4 hours following dosing and twice daily thereafter for a total of 14 days.
- Frequency of weighing: Body weights were recorded immediately prior to dosing (control weight) and at 7 and 14 days.
Statistics:
95% confidence limits
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
2 130 mg/kg bw
Based on:
test mat.
95% CL:
1 698 - 2 671
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
3 083 mg/kg bw
Based on:
test mat.
95% CL:
2 458 - 3 866
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 562 mg/kg bw
Based on:
test mat.
95% CL:
2 153 - 3 050
Mortality:
see any other information on results
Clinical signs:
not described
Body weight:
The body weight gain was reduced in one female between day 7 and 14.
Gross pathology:
not investigated
Other findings:
no

Time of Observation

Number of Deaths

Dosage Level (mg/ kg)

807.1

1281

2034

3229

5126

M

F

M

F

M

F

M

F

M

F

0 – 4 hours

 

 

 

 

 

 

 

 

2

2

Day 1

 

 

 

 

1

 

4

2

3

3

Day 2

 

 

 

 

1

 

 

1

 

 

Day 3

 

 

 

 

 

 

1

 

 

 

Day 4 -14

 

 

 

 

 

 

 

 

 

 

Total

0/5

0/5

0/5

0/5

2/5

0/5

5/5

3/5

5/5

5/5

Interpretation of results:
not classified
Conclusions:
Based upon the data obtained, the acute oral LD50 values and 95% confidence limits for the test material (75% act. ingr.) were calculated to be as follows: Male Rats: 2130 (1698 - 2671) mg/kg bw, Female Rats: 3083 (2458 - 3866) mg/kg bw, Combined Male and Female Rats: 2562 (2153 - 3050) mg/kg bw. For a mixture containing 50% active ingredient the acute oral LD50 values are expected to be 3195 mg/kg bw (males), 4624.5 mg/kg bw (females) and 3843 mg/kg bw (combined males and females).
Executive summary:

An acute oral toxicity study was performed in 25 male and 25 female rats of the Sprague-Dawley strain, obtained from Harlan Industries. The test material, 75% TBPA in Shellsol 71, was administered orally by gavage as a solution in corn oil at the following dosage levels: 807.1, 1281, 2034, 3229 and 5126 mg/kg bw. Five rats of each sex were used at each dosage level. Water and diet were available ad libitum, except for an overnight period of approximately 18 hours immediately preceding oral administration during which food, but not water, was withheld. The rats were observed for mortality, only, during the first 4 hours following dosing and twice daily thereafter for a total of 14 days. Mortality was observed within 3 days at the dosage levels of 2034, 3229 and 5126 mg/kg bw. The acute oral LD50 values are 2130 mg/kg bw (males), 3083 mg/kg bw (females) and 2562 mg/kg bw (combined males and females). For a mixture containing 50% active ingredient the acute oral LD50 values are calculated to be 3195 mg/kg bw (males), 4624.5 mg/kg bw (females) and 3843 mg/kg bw (combined males and females).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 843 mg/kg bw
Quality of whole database:
similar to OECD guideline

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978-12-28 and 1979-02-07
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Charles River CD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Weight at study initiation: male: 226 to 300 g
- Housing: group-housed during the quarantine period; housed individually in wire-mesh cages throughout the postexposure period
- Diet and water: Purina Laboratory Chow and water, e.g. ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature and humidity: in accordance with standard outlined in the "Guide for the Care and Use of Laboratory Animals; DHEW No. (N.I.H. 74-23) 1974"
Route of administration:
other: inhalation: aerosols and vapors
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: FMI LAB pump
- Exposure chamber volume: 160 L cubical, stainless steel and glass chamber
- Method of holding animals in test chamber: individually
- Rate of air: 8 L/min
- pressure in air chamber: 10 psig
- Treatment of exhaust air: chamber exhaust was filtered with an activated charcoal filter and a Cambridge Absolute filter
Analytical verification of test atmosphere concentrations:
no
Remarks:
The individual concentrations of the compound in the chamber atmosphere were calculated from the ratio of the rate of aerosol dissemination to the rate of total chamber airflow.
Duration of exposure:
4 h
Concentrations:
calculated chamber conc. [mg/L]: 2.06, 4.85, 5.49, 6.34, 20.59
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for pharmacotoxic signs and mortality were made during and immediately following the 4-hour exposure period and twice daily thereafter for 14 days. Body weights were recorced prior to the 4-hour exposure and periodically thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Preliminary study:
No preliminary study
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
6.1 mg/L air
Based on:
test mat.
95% CL:
5.65 - 6.59
Exp. duration:
4 h
Mortality:
20.59 mg/L: all animals (5 males/5 females) died during the 14 day study period
6.34 mg/L: 7 animals (5 males/ 2 females) died during the 14 day study period
5.49 mg/L: 2 animals (1 male/ 1 female) died during the 14 day study period
4.85 mg/L: 1 male died during the 14 day study period
Clinical signs:
other: During exposure, salivation, nasal discharge, eye squint and dyspena were observed. At the high level, gasping and cloudy eyes were also observed.
Body weight:
20.59 mg/L: body weight loss was observed for 4 females on day 1 postexposure
6.34 mg/L: slight body weight loss was observed on day 1 postexposure
5.49 mg/L: slight body weight loss was observed, especially in the female rats
4.85 mg/L: a slight to moderate body weight loss was observed in all surviving rats
2.06 mg/L: no body weight effects were observed
Gross pathology:
Necropsy of the rats that died spontaneously revealed dark pink lungs (some wih red foci), red patchy lungs or clear fluid in the chest cavity. In addition, there were isolated cases of reddish urine in the bladder, hollow kidney, air-distened stomach and dark foci on the stomach mucosa. Necropsy of the animals sacrificed at the end of the observation periods revealed red patchy lungs in one rat, a brown hollow kidney in three rats and no gross lesions in 26 rats.
Interpretation of results:
Toxicity Category III
Conclusions:
The LC50 value was calculated to be 6.1 mg/L (vapors + aerosol) for the test material (75% active ingredient). Therefore, the acute LC50 value is expected to be 9.2 mg/L for the test material which contains 50% of the active ingr.
Executive summary:

The acute inhalation toxicity of t-butyl peracetate was studied in rats by exposing male and female rats for four hours to vapours and aerosols of the test material (75% t-buty peracetate in Shellsol 71). The five nominal exposure concentrations were 2.06, 4.85, 5.49, 6.34 and 20.59 mg/L, which resulted in 0, 1, 2, 7 and 10 deaths, respectively. The 4 -hour LC50 was calculated to be 6.1 mg/L (vapours + aerosol). Therefore, the acute LC50 value is expected to be 9.2 mg/L for the test material which contains 50% of the active ingr.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
9 200 mg/m³
Quality of whole database:
The study was equivalent to OECD guidline 403.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978-08-23 and 1978-12-15
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
2 animals per doses per sex
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: H.A.R.E. Rabbits for Research, Hewitt, New Jersey
- Weight at study initiation: 2304 to 2863 grams
- Housing: individually housed in hanging wire-mesh cages
- Diet: Purina® Rabbit Chow®; ad libitum
- Water: ad libitum
- Acclimation period: 19 days
Type of coverage:
occlusive
Vehicle:
not specified
Details on dermal exposure:
TEST SITE
The hair was removed from the back of each rabbit (20-30% of the body surface) with an electric clipper. The skin of one male and one female in each group was abraded with a scalpel blade by making 10 cm long epidermal abrasions every 2 or 3 cm longitudinally over the area of exposure. Following dosing, the application sites were wrapped with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with several layers of 75 mm Elastoplast tape. A collar was also applied.

REMOVAL OF TEST SUBSTANCE
- 24-h following application, the bandages and collars were removed and the test sites were wiped clean
Duration of exposure:
24 hours
Doses:
500, 1000, 2000, 4000, 8000 and 16000 mg/kg
No. of animals per sex per dose:
2
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: rabbits were observed for mortality twice daily for a total of 14 days
- Frequency of weighing: immediately prior to test material administration (control weight) and at 7 and 14 days of the observation period

Statistics:
95% confidence limits
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
4 000 mg/kg bw
Based on:
test mat.
95% CL:
2 000 - 8 000
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
5 657 mg/kg bw
Based on:
test mat.
95% CL:
2 828 - 11 314
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 757 mg/kg bw
Based on:
test mat.
95% CL:
3 364 - 6 727
Mortality:
see any other information on results
Body weight:
The body weight gain of two females was slightly reduced between day 7 and 14. Two other females lost weight between day 1 and 14. One male showed a very slight lost of weight between day 1 and 7. The body weights of all animals are shown in table 2 in the section any other information on results.

Table 1 shows the number of deaths during the observation period.

Table 1:

Time of observation

Number of Deaths

Dosage Level (mg/kg)

500

1000

2000

4000

8000

16000

M

F

M

F

M

F

M

F

M

F

M

F

Day 1

 

 

 

 

 

 

 

 

2

1

2

1

Day 2

 

 

 

 

 

 

1

 

 

1

 

 

Day 3 -14

 

 

 

 

 

 

 

 

 

 

 

 

Total

0/2

   0/2

0/2

   0/2

0/2

   0/2

1/2

   0/2

2/2

   2/2

2/2

   2/2

M: male

F: female

Table 2 shows the body weights obtained during the observation period.

Table 2:

Dosage Level (mg/kg)

Animal + Sex

Control Weight (g)

7 Day Weight

(g)

14 Day Weight (g)

500

01 Male

2304

2441

2841

02 Male

2512

2668

2761

01 Female

2525

2731

3088

02 Female

2852

2939

3131

1000

03 Male

2545

2706

2841

04 Male

2429

2442

2530

03 Female

2693

2732

2611

04 Female

2485

2505

2981

2000

05 Male

2310

2421

2733

06 Male

2863

2841

2889

05 Female

2742

2886

2863

06 Female

2358

2205

1971

4000

07 Male

2470

2460

2581

08 Male

2320

died

died

07 Female

2633

2565

2911

08 Female

2569

2211

2423

8000

09 Male

2480

died

died

10 Male

2402

died

died

09 Female

2451

died

died

10 Female

2325

died

died

16000

11 Male

2326

died

died

12 Male

2467

died

died

11 Female

2310

died

died

12 Female

2308

died

died

Interpretation of results:
not classified
Conclusions:
Based upon the data obtained, the acute dermal LD50 values and 95% confidence limits for the test material (75% active ingredient) were calculated to be as follows: Male Rabbits: 4000 (2000 - 8000) mg/kg bw, Female Rabbits: 5657 (2828 - 11314) mg/kg bw, Combined Male and Female Rabbits: 4757 (3364 - 6727) mg/kg bw. Based on the mixture containing 50% of the active ingredient the dermal LC50 values are expected to be 6000 mg/kg bw (males), 8485.5 mg/kg bw (females) and 7135.5 mg/kg bw (combined male and female).
Executive summary:

An acute dermal toxicity study was performed in 12 male and 12 female New Zealand White rabbits obtained from H.A.R.E. Rabbits for Research, Hewitt, New Jersey.They were individually housed in hanging wire-mesh cages and water and diet were available ad libitum. The rabbits were divided into six groups of two male and two female rabbits each. The test material (75% active ingredient) was applied once only to the backs of the rabbits at the following dosage levels: 500, 1000, 2000, 4000, 8000 and 16000 mg/kg bw. Following dosing, the application sites were wrapped with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with several layers of 75 mm Elastoplast tape. The animals were durated for 24 hours. The mortality was checked twice daily for a period of 14 days. The body weight gain were recorded immediately prior to test material (control weight) and on day 7 and 14.

Based upon the data obtained, the acute dermal LD50 values and 95% confidence limits were calculated to be as follows: Male Rabbits: 4000 (2000 - 8000) mg/kg bw, Female Rabbits: 5657 (2828 - 11314) mg/kg bw, Combined Male and Female Rabbits: 4757 (3364 - 6727) mg/kg bw. Based on the mixture containing 50% of the active ingredient the dermal LC50 values are expected to be 6000 mg/kg bw (males), 8485.5 mg/kg bw (females) and 7135.5 mg/kg bw (combined male and female).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
7 135.5 mg/kg bw
Quality of whole database:
similar OECD guideline

Additional information

Acute oral toxicity study:

An acute oral toxicity study was performed in 25 male and 25 female rats of the Sprague-Dawley strain, obtained from Harlan Industries. The test material, tert-buty peracetate, was administered orally by gavage as a solution in corn oil at the following dosage levels: 807.1, 1281, 2034, 3229 and 5126 mg/kg. Five rats of each sex were used at each dosage level. Water and diet were available ad libitum, except for an overnight period of approximately 18 hours immediately preceding oral administration during which food, but not water, was withheld. The rats were observed for mortality, only, during the first 4 hours following dosing and twice daily thereafter for a total of 14 days. Mortality was observed within 3 days at the dosage levels of 2034, 3229 and 5126 mg/kg. The acute oral LD50 values are 2130 mg/kg bw (males), 3083 mg/kg bw (females) and 2562 mg/kg bw (combined males and females). For a mixture containing 50% active ingredient the acute oral LD50 values are calculated to be 3195 mg/kg bw (males), 4624.5 mg/kg bw (females) and 3843 mg/kg bw (combined males and females).

Acute inhalation toxicity study:

Key study

The acute inhalation toxicity of t-butyl peracetate was studied in rats by exposing male and female rats for four hours to vapours and aerosols of t-buty peracetate. The five nominal exposure concentrations were 2.06, 4.85, 5.49, 6.34 and 20.59 mg/L, which resulted in 0, 1, 2, 7 and 10 deaths, respectively. The 4 -hour LC50 was calculated to be 6.1 mg/L as vapour or aerosol (6000 mg/ cubic meter). Therefore, the acute LC50 value is expected to be 9.2 mg/L (9200 mg/cubic meter) for the test material which contains 50% of the active ingredient.

Supporting study

The acute inhalation toxicity of the test material (50% t-butyl peroxyacetate in Shellsol T) was studied in rats by exposing them for eight hours to vapour of the substance, containing tert-butyl peroxyacetate at various concentrations ranging from 3 to 1102 ppm. This study was similar to OECD guideline, however the exposure time was 8 hours instead of 4 hours. No deleterious effects were observed in rats exposed for eight hours to t-butyl peroxyacetate at concentrations of up to 29 ppm. The 8 -hour LC50 of t-butyl peroxyacetate was 450 ppm (analytical conc. 2.4 mg/L) based on the act. ingr. Therefore, the LC50 value for the test material (50% act. ingr. in Shellsol T) is expected to be 4.8 mg/L.

Gage (1970) reviewed the subacute inhalation toxicity of 109 industrial chemicals. To study the acute inhalation toxicity of 50 % tert-butyl peracetate in dimethyl phtalate (w/w), 2 male and 2 female rats ( Alderley Park) were exposed to 30 ppm (corresponding to 0.16 mg/L) of saturated vapour of the test substance for 4 hours. Nose irritation, respiratory difficulty and lung oedema were observed. The reliability of this publication is not assignable due to no sufficient experimental details.

Acute dermal toxicity study

An acute dermal toxicity study was performed in 12 male and 12 female New Zealand White rabbits obtained from H.A.R.E. Rabbits for Research, Hewitt, New Jersey.They were individually housed in hanging wire-mesh cages and water and diet were available ad libitum. The rabbits were divided into six groups of two male and two female rabbits each. The test material was applied once only to the backs of the rabbits at the following dosage levels: 500, 1000, 2000, 4000, 8000 and 16000 mg/kg bw. Following dosing, the application sites were wrapped with gauze bandaging and overwrapped with Saran Wrap. The entire application area was then wrapped with several layers of 75 mm Elastoplast tape. The animals were durated for 24 hours. The mortality was checked twice daily for a period of 14 days. The body weight gain were recorded immediately prior to test material (control weight) and on day 7 and 14.

Based upon the data obtained, the acute dermal LD50 values and 95% confidence limits were calculated to be as follows: Male Rabbits: 4000 (2000 - 8000) mg/kg bw, Female Rabbits: 5657 (2828 - 11314) mg/kg bw, Combined Male and Female Rabbits: 4757 (3364 - 6727) mg/kg bw.

Based on the mixture containing 50% of the active ingredient the dermal LC50 values are expected to be 6000 mg/kg bw (males), 8485.5 mg/kg bw (females) and 7135.5 mg/kg bw (combined males and females).


Justification for selection of acute toxicity – oral endpoint
only one available study

Justification for selection of acute toxicity – inhalation endpoint
Study of more current date was chosen. The study fulfills the criteria of the OECD guidline.

Justification for selection of acute toxicity – dermal endpoint
only one available study

Justification for classification or non-classification

Acute oral and dermal toxicity:

Based on the results, the test substance is not considered to be classified for acute oral and dermal toxicity according to Regulation (EC) No 1272/2008.

Acute inhalation toxicity study:

Based on the results of the key study, the test substance is classified and labelled for acute inhalation toxicity cat. 3 (H331: toxic if inhaled) and R20 (harmful by inhalation) according to Regulation (EC) No 1272/2008 (CLP).

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