Acetophenone

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

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

Test material information

Constituent 1

Reference substance name:

Acetophenone

EC Number:

202-708-7

EC Name:

Acetophenone

Cas Number:

98-86-2

Molecular formula:

C8H8O

IUPAC Name:

1-phenylethanone

Details on test material:

- Name of test material (as cited in study report): 39280 R.P., pure acetophenone
- Analytical purity: 99.7%
- Batch No. 77258

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 application
- 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

Based on:

test mat.

Mortality:

3 g/kg: 3/10; 4 and 5.2 g/kg: all rats died (for details see Table 1)

Clinical signs:

other: see Table 1

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:

Category 5 based on GHS criteria

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.