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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study with test protocol similar to OECD guideline 402 with acceptable deviations: less detailed documentation of testing procedure, no microscopic examination, confidence interval not specified; sufficient documentation of test results; study acceptable for assessment
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
(less detailed documentation of testing procedure, no microscopic examination, confidence interval not specified)
Principles of method if other than guideline:
5 doses of acetophenone covering a dose range of 1.82-5.2 g/kg were dermally applied with occclusion to groups of 5 male and 5 female rats. Mortality, clinical symptoms and weight development were observed for up to 15 days. All animals found dead and survivors sacrificed on day 15 p.a. were subjected to an autopsy with macroscopic examination of the principal viscera in abdomen and thorax.
GLP compliance:
no
Test type:
standard acute method

Test material

Constituent 1
Chemical structure
Reference substance name:
Acetophenone
EC Number:
202-708-7
EC Name:
Acetophenone
Cas Number:
98-86-2
Molecular formula:
C8H8O
IUPAC Name:
1-phenylethan-1-one
Details on test material:
- Name of test material (as cited in study report): 39280 R.P., pure acetophenone
- Analytical purity: 99.7%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: IFFA CREDO
- Weight at study initiation: 130-150 g
- Fasting period before study: no data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 6 x 6 cm
- % coverage: not specified
- Type of wrap if used: aluminium foil and sparadrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with soap water
- Time after start of exposure: 24 hrs
Duration of exposure:
24 hrs
Doses:
1,82, 2,36, 3, 4, 5,2 g/kg
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days post apllication
- Frequency of observations and weighing: clinical signs daily, body weight on day 0, 5, 10 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination of viscera in abdomen and thorax
Statistics:
Statistically significant difference of body weight development with p<0.05, p<0.01 (statistical method not specified)
LD50 calculated by method of Dragstedt and Lang

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3 300 mg/kg bw
Mortality:
3 g/kg: 3/10; 4 and 5.2 g/kg: all rats died (for details see Table 1)
Clinical signs:
see Table 1
Body weight:
2.36 g/kg: significant decrease on day 5 p.a. (for details see Table 1)
No data for other dose groups
Gross pathology:
Jejunum and ileum identified as target after dermal application

Any other information on results incl. tables

Table 1: Findings after acute dermal application of acetophenone to rats

Dose group

(g/kg)

Mortality

Clinical symptoms

Autopsy

Body weight (g)

Incidence

Time to death p.a.

Timepoint p.a.

Symptoms

Day 0

Day 5

Day 10

Day 15

0

0/10

-

140.5 ±5

167.2±8.7

184.2±17

221±22.9

1.82

0/10

1-2 hrs in 5/10, 1-24 hrs in 5/10

From 6 hrs

Reduced spontaneous activity

Prostration (1/10) and palpebral ptosis (10/10)

No macroscopic findings

2.36

0/10

Up to 48 hrs

Up to 72 hrs

Reduced spontaneous activity with staggering gait, lacrimation

palpebral ptosis (10/10)

9/10: congestion of mucous layer of jejunum; yellowish liquid in a part of the jejunum

137.3±4.2

155.5±8.4*

175±15

212.5±22.4

3

3/10

6 hrs – 6 d

Up to 5 d

2 hrs – 2 d


6 hrs – 5 d

Reduced spontaneous activity

staggering gait, prostration, tremor; lacrimation, palpebral ptosis

Flat and halting breath

1/10 loss of weight and cyanosis on day 5, death on day 6

6/7 survivors: mucous intestinal congestion, 2/7 thinning of the abdominal lining in the region of jejunum and ileum, yellowish liquid present

4

10/10

6-48 hrs

From start of exposure

Staggering gait, prostration and inhibition of turn-around reflex, piloerection, lacrimation, palpebral ptosis, flat breath

No macroscopic findings

5.2

10/10

2-24 hrs

0 min up to death

Same as 4 g/kg

No macroscopic findings

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
With a LD50 of 3.300 mg/kg in rats, acetophenone showed only very slight toxicity after dermal exposure. Clinical symptoms were typical of effects on the nervous symptoms and on the eyes with a LOAEL of 1820 mg/kg. Autopsy revealed the intestinal tract (jejunum and ileum) to be a target of the adverse action of acetophenone with a LOAEL of 2360 mg/kg.
Executive summary:

5 doses of acetophenone ranging from 1.82-5.2 g/kg were applied dermally with occclusion to groups of 5 male and 5 female rats. Mortality, clinical symptoms and weight development were observed for up to 15 days. All animals found dead and survivors sacrificed on day 15 p.a. were subjected to an autopsy with macroscopic examination of the principal viscera in abdomen and thorax. With a LD50 of 3.300 mg/kg in rats, acetophenone showed only very slight toxicity after dermal exposure. Clinical symptoms were typical of effects on the nervous symptoms and on the eyes with a LOAEL of 1820 mg/kg. Autopsy revealed the intestinal tract (jejunum and ileum) to be a target of the adverse action of acetophenone with a LOAEL of 2360 mg/kg.