Methyl benzoylformate

Endpoint summary

Description of key information

All key information presented in this section was conducted to (or is considered equivalent to) international testing guidelines. GLP certification is appropriate to the age of the studies and the testing dates.

Acute toxicity: inhalation

Data waiving, exposure considerations.  The study need not be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles of an inhalable size.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

reporting details

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
- Weight at study initiation: mean: males: 200g; females: 168g

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

0.5% aqueous CMC + 2-3 drops Cremophor EL

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 - 31,6%

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg

Doses:

10000, 6810, 4640, 3160 mg/kg bw

No. of animals per sex per dose:

5 per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations were done daily; weighing was done on day 4, 7 and 12
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Sex:

male/female

Dose descriptor:

LD50

Effect level:

6 800 - 10 000 mg/kg bw

Based on:

test mat.

Mortality:

At 10000 mg/kg bw day: Within 48 hours all male rats died. 7 days after application 4 of 5 female rats were dead. For details see table 1.

Clinical signs:

other: Highest Dose (10000 mg/kg): All animals showed in the highest dose apathy and staggering until day two after application. Prone/lateral position was seen until 2 hours after application of test substance. 2 hours after application animals showed atonia, n

Gross pathology:

All animals which were sacrificed scheduled showed normal organs without abnormality.
In the animals found dead (higest dose): the heart showed an acute dilatation and hyperemia. In the liver a centrilobular lobe outline is seen. The lungs of 2 rats showed slight edema.

Table 1: Mortality:

			died within
Dose [mg/kg]	conc [%]	animal #	1h	24h	48 h	7 d	14 d
10000	50	5 male	0/5	4/5	5/5	5/5	5/5
		5 female	0/5	2/5	3/5	4/5	4/5
6810	50	5 male	0/5	0/5	0/5	0/5	0/5
		5 female	0/5	0/5	0/5	0/5	0/5
4640	46,4	5 male	0/5	0/5	0/5	0/5	0/5
		5 female	0/5	0/5	0/5	0/5	0/5
3160	31,6	5 male	0/5	0/5	0/5	0/5	0/5
		5 female	0/5	0/5	0/5	0/5	0/5

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of the test substance is 6800-10000 mg/kg bw, therefore the test material is not classified as acutely toxic via the oral route in accordance with the cirtiera of EU regulatio n 1272/2008.

Executive summary:

In this study (equivalent to OECD 401), the acute oral LD50 of the test material (EC 239-263-3) was determined to be 6800 -10000 mg/kg bw (male & female) in the Rat. The LD50 is based upon the actual level of test material administered (gavage). The study was conducted prior to the adoption of GLP criteria and certification, but is considered reliable with restrictions (2) (according to Klimisch et al, 1997) based upon the level of reporting. This LD50 value is outside the range for classification as an acute toxic substance according to EU regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

6 800 mg/kg bw

Quality of whole database:

1

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

other justification

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Quality of whole database:

1

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:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: male animals approx. 8 - 10 weeks, female animals approx. 12 - 14 weeks
- Weight at study initiation: 200-300g
- Housing: singly
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5d
- Fasting: 16h before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 30-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal and dorsolaterale parts of the trunk
- % coverage: 10

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing of the application site with luke warm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1.75 ml/kg bw
- Concentration (if solution): 100%
- Constant volume or concentration used: yes

For a better homogeneity the test item will be heated at 40°C for approx. 1 hour. The test item will be administrated hand warm.

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals will be observed individually for behaviour changes or signs of toxicity <0.5, 1, 2, 3, 4 and 5 hours after dosing at the day of administration and at least once daily thereafter. Clinical observations will be performed at least once each working-day and recorded individually. Individual body weight will be determined shortly before test item administration, at weekly intervals thereafter and before the sacrifice of the animals at the end of the observation period. Moreover, the body weights of animals that die or are sacrificed in a moribund state will be determined from study day 1, onward. A check for moribund and dead animals will be made at least once each workday.
- scoring: Individual recording of findings 30 - 60 minutes after removal of the semi- occlusive dressing; afterward, at approx. weekly intervals and on the last day of observation.
- Necropsy of survivors performed: yes
- Other examinations performed: On the last day of the observation period, the animals will be sacrificed by CO2-inhalation in a chamber with increasing concentrations over time, followed by necropsy and gross-pathological examination. All animals that die will be necropsied as early as possible after death.

Statistics:

no

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality observed.

Clinical signs:

other: No systemic clinical signs were observed during clinical examination.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study.

Other findings:

In all male animals well-defined erythema (grade 2) was noted on study day 1 and persisted in four of these animals until study day 3. Thereafter, very slight erythema (grade 1) was noted in these four animals from study day 6 until study day 7 or 8. In the fifth animal very slight erythema was seen from day 2 until day 8. Very slight edema (grade 1) was noted in all male animals on study day 1 only. Scaling was noted in three male animals from study day 7 or 8 until study day 10 after application.

In two females well-defined erythema (grade 2) was noted on study day 1, but decreased to very slight erythema (grade 1) in one of these animals and was noted from study day 2 until study day 7. In these two females very slight edema (grade 1) was seen on study day 1 after application only.
In the three remaining female animals very slight erythema (grade 1) was noted on study day 1, only.

Interpretation of results:

GHS criteria not met

Conclusions:

The test material has an LD50 of >2000 mg/kg bw for acute dermal toxicity. This test value does not fulfill the criteria for classification and labelling according to EU regulation 1272/2008.

Executive summary:

In this guideline study (OECD 403) conducted with GLP certification, the acute dermal LD50 of the test material (EC 239-263-3) was determined to be >2000 mg/kg bw in the Rat. Test animals were exposed for 24 hours with a semiocclusive bandage. The test material was administered unchanged. The test material is not classified as acutely toxic according to the EU Classification, Labelling, and Packaging (CLP) regulation (1272/2008), based upon this result.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

1

Additional information

Acute Toxicity: Oral

The test item was administered by gavage to male and female Wistar rats at concentrations of 10000, 6810, 4640, 3160 mg/kg bw. The animals were observed for 14 days. Mortality, body weight and clinical signs were recorded continuously. Organ weighing and gross necropsy was performed after scheduled sacrifice. Mortality occurred at the highest dose level. Body weight and body weight gain were comparable to control animals. All animals of the 10.000 mg/kg bw group showed apathy and staggering until day two after application. Prone/lateral position was seen until 2 hours after application of test substance. 2 hours after application animals showed atonia, narcotic like symptoms and loss of pain reflex. Until day 2 after application all animals showed piloerection and smeared fur within urine. Salivation was seen until 30 min after application. The animals showed a bad general state of health until day 2 after application. At 6810 mg/kg all animals showed apathy and staggering until 4-5 hours after application. Until 5 hours after application all animals showed redness of skin. Exphtalmia was seen the first 30 minutes after application. The animals showed a bad general state of health until 5 hours after application. All animals of the 4640 mg/kg bw group showed apathy and staggering until 1-2 hours after application. Exphtalmia was seen the first 15 minutes after application. The animals showed a bad general state of health until 2 hours after application. At 3160 mg/kg, all animals showed staggering until 1 hour after application. The animals showed a light bad general state of health until 1 hour after application. The LD50 is therefore considered to be > 5000 mg/kg bw.

Acute Toxicity: Dermal

In an acute dermal toxicity study (Limit Test), young adult Wistar rats(5 males and 5 females)were dermally exposed to a single dose of 2000 mg/kg bw of the undiluted test item to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours (OECD 402, GLP). The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred. No clinical signs were observed. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study. Accordingly, the acute dermal median lethal dose (LD₅₀) was determined to be LD₅₀, dermal, rat > 2000 mg/kg bw.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is not considered to be classified for acute oral toxicity under Regulation (EC) No. 1272/2008.