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Description of key information

In an acute oral toxicity study with the rat the LD50 of BMDBM was greater than 16000 mg/kg bw . No dermal toxicity effects up to the maximum applied dose of 1000 mg/kg bw were observed in an acute dermal toxicity study with the rat. No study on inhalation toxicity of BMDBM is available.

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Comparable to guideline study with acceptable restrictions.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
limit dose of 16000 mg/kg bw
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: W. Gassner, Sulzfeld, Germany
- Weight at study initiation: 90 - 115 g
- Fasting period before study: 16 h
- Housing: 5 animals per Makrolon Type III cage with autoclaved sawdust as bedding
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): 55 ± 5 %
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
other: 4 % w/v aqueous gum arabic solution
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40 % w/v as suspension
- Amount of vehicle: 40 mL/kg bw
Doses:
limit dose of 16000 mg/kg bw
No. of animals per sex per dose:
10 males and 10 females
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: frequently on the day of dosing and daily thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (5 males and 5 females of the treated group and all organs with abnormal macroscopic appearance)
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 16 000 mg/kg bw
Remarks on result:
other: all animals survived at this dose
Mortality:
There were no mortalities in either the treated or control group.
Clinical signs:
Signs of reaction to treatment, observed shortly after dosing included pitoerection (only in control animals) and abnormal body carriage (hunched posture). These signs were accompanied by slight lethargy immediately after dosing in male rats only.
Recovery, as judged by external appearance and behaviour, was apparently complete within 5 days after treatment.
Body weight:
Body weight gains in all treated rats were comparable with those of the control animals throughout the two week observation period.
Gross pathology:
Autopsy findings for rats killed at termination were considered to be normal.
Other findings:
HISTOPATHOLOGY:
The marked loss of sperm as well as the accumulation of cellular debris in the epididymal tubules of the 5 males examined and the slight vacuolation of hepatocytes (3 male and 2 female animals) may be attributable to treatment with butyl methoxydibenzoylmethane (BMDBM). The testes of all examined animals appeared normal.
Hemosiderin deposits occur commonly in the spleen of rats whereas hemopoiesis in the same organ occurs at a time of stress. Furthermore, the spleen is a hemopoietic organ in the embryo and up some weeks after birth. So indications of spleen hemopoiesis could also be remains of animal development. Unfortunately, no data of control animals were provided for comparison, so that attributing these findings uniquely to BMDBM treatment is not justified. Peribronchial lymphoid hyperplasia and focal interstitial pneumonitis are stages of evolution of chronic murine pneumonia. Small round infiltrates in the liver and focal interstitial nephritis may be considered as a bacterial infection.
Mitotic cells in kidneys, liver, stomach, duodenum, pancreas, adrenals, and epididymis are signs of growing organs.

Table 2: Acute toxicity signs as reaction to treatment with BMDBM

Day

Control

Males

Control

Females

16000 mg/kg bw

Males

16000 mg/kg bw

Females

1

15A

15A

15A / 21A / 1A

15B / 21A

15A

15A

15A

15B

15A

15A

15A

15B

2

15A

15A

15A

15B

3

15A

15A

15A

15B

4

N

N

N

15A

5

N

N

N

N

6-14

N

N

N

N

Signs of toxicity coding: 1. Lethargy, 15. Piloerection, 21. Hunched posture

Degree of reaction: A = slight, B = Moderate, C = Severe, N = No abnormalities detected

 

Table 3: Body weight gains of rates dosed once with BMDBM

Group

Sex

Bodyweight [g]a)

Bodyweight gain [g]

Day 1

Day 8

Day 15

Control

Male

108

167

214

106

Female

99

152

178

79

16000 mg/kg bw

Male

106

166

218

112

Female

101

151

175

74

a)Average of 10 animals per group per sex

 

Table 4: Autopsy findings after acute oral toxicity study with BMDBM

Group

Sex

Organs examined

Autopsy findings

Control

Male

As listed in table 1

Within normal limits

Female

As listed in table 1

Within normal limits

16000 mg/kg bw

Male

As listed in table 1

Within normal limits

Female

As listed in table 1

Within normal limits

Interpretation of results:
GHS criteria not met
Conclusions:
After oral administration of 16000 mg/kg bw of BMDBM as suspension in 4 % gum arabic in water w/v to male and female rats, no mortality was observed.
Executive summary:

Oral application of a suspension containing 16000 mg/kg bw by gavage to male and female rats resulted in no mortality within 14 days of post-observation. Also vehicle-treated animals showed no mortality. Both groups exhibited clinical signs in the first 4 days after treatment of which the most abundant was piloerection; the animals treated with BMDBM but not the controls showed signs of lethargy and hunched posture. Body weights and gross necropsy were in normal limits in all animals. Histopathological changes were observed mainly in the epididymes and spleen of treated animals, but no causal connection could be developed as animals suffered from a bacterial infection and pneumonia.

Taken together, the test item BMDBM has a LD50 (rat, oral) of >16000 mg/kg bw and therefore does not need to be classified under GHS and CLP.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
exposure considerations
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
Clinical signs:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Comparable to guideline study with acceptable restrictions.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
only 2 dose levels examined
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: Füllinsdorf Albino SPF rats
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Füllinsdorf, Switzerland
- Weight at study initiation: 194 - 212 g
- Acclimation period: 6 d

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): 55 ± 5 °C
Type of coverage:
occlusive
Vehicle:
other: carbitol
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lumbal
- % coverage: approximately 10 % of body surface
- Type of wrap if used: gauze, pergamine paper and occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Concentration: 0, 500, and 1000 mg/kg bw
- For solids, paste formed: yes, at the highest concentration
Duration of exposure:
24h
Doses:
0, 500, and 1000 mg/kg bw
No. of animals per sex per dose:
5 male and 5 female animals per dose group.
Control animals:
yes, concurrent vehicle
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no deaths at highest dose level 1000 mg/kg bw
Mortality:
No mortalities were recorded during the 14 day observation period.
Clinical signs:
Females: slight (grade 1) to moderate (grade 3) erythema were detected in 4 animals of the control group on days 1 and 4. With 500 mg/kg all 5 animals showed slight erythema on day 4. With 1000 mg/kg only one animal was detected with well defined erythema (grade 2). Edemas were not detected in females.
Males: In all groups neither erythema nor edemas were found throughout the experiment.
Body weight:
Body weight had in all groups decreased during the 24 h of dermal exposure in the occlusive dressing. Further body weight development was normal.
Gross pathology:
At final autopsy 2 males and 1 female of the 1000 mg/kg group were detected with dark spots on one or both kidneys. Histological examination considered them as non-pathological. No further anomalies were found.

Table 1: Bodyweights of male rats dermally treated with butyl methoxydibenzoylmethane.

Day

Bodyweight [g]

0 mg/kg bw

500 mg/kg bw

1000 mg/kg bw

0

208.0 ± 11.9

212.8 ± 5.9

213.6 ± 9.6

1

197.8 ± 14.6

205.2 ± 9.1

209.8 ± 8.3

2

206.0 ± 14.1

214.2 ± 9.9

210.2 ± 11.1

5

225.4 ± 16.3

238.0 ± 13.9

235.8 ± 14.9

6

229.2 ± 19.6

242.0 ± 14.1

240.8 ± 15.4

7

234.8 ± 19.0

246.8 ± 15.3

247.0 ± 17.4

8

238.2 ± 19.2

252.6 ± 16.3

250.6 ± 17.7

14

262.0 ± 24.7

279.6 ± 19.0

273.2 ± 24.7

15

270.6 ± 27.6

287.6 ± 21.5

279.8 ± 25.1

 

Table 2: Bodyweights of female rats dermally treated with butyl methoxydibenzoylmethane.

Day

Bodyweight [g]

0 mg/kg bw

500 mg/kg bw

1000 mg/kg bw

0

198.0 ± 7.1

198.2 ± 8.8

189.8 ± 5.0

1

190.4 ± 8.1

191.2 ± 10.7

184.4 ± 5.0

4

198.4 ± 7.6

2.2.4 ± 10.8

194.0 ± 4.7

5

198.6 ± 8.3

205.6 ± 11.7

195.0 ± 3.4

6

201.6 ± 8.6

07.6 ± 13.6

194.0 ± 2.9

7

203.8 ± 10.6

210.2 ± 13.6

198.8 ± 2.9

8

205.6 ± 11.9

210.8 ± 12.7

198.8 ± 5.8

13

212.0 ± 8.4

220.2 ± 14.8

208.0 ± 3.7

15

216.0 ± 11.5

229.0 ± 18.2

212.4 ± 4.3

 

Interpretation of results:
GHS criteria not met
Conclusions:
Test item BMDBM was applied to rats up maximum to 1000 mg/kg, since the mode of application was limited by the consistence of the suspension with Carbitol. No mortalities reported.
Executive summary:

Suspensions containing 20 % and 40 % butyl methoxydibenzoylmethane (BMDBM) in Carbitol (w/v) were prepared for a single dermal application of 500 and 1000 mg/kg. The sample with maximum dosis had the consistence of a paste. Control groups were treated with Carbitol only.

Except one initial decrease during the day of dermal exposure body weight development during the following 14-day observation period was in all groups normal. No deaths were found. In female groups slight to moderate erythema were detected up to 4 days after exposure. Four cases were from the control group, five from the low dosis group and one from the high dosis group. Except one animal in the control group which was classified as the most severe case (medium erythema) all others were of slight to well defined grade. It can be assumed that Carbitol has an irritative effect on the skin of female rats since frequency and severity of erythema among the 3 groups rather reflect the amount of solvent than the test substance. In all male groups no skin reactions were observed. No edemas were detected neither in male nor female groups. Final autopsy showed no abnormalities, except 3 animals with a few dark spots on kidneys, which after histological examination were not characterized pathological.

Test item BMDBM was applied to rats up maximum to 1000 mg/kg, since the mode of application was limited by the consistence of the suspension with Carbitol. No mortalities reported.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Evaluating the study of Buser (1980) it is visible that acute oral toxicity of butyl methoxydibenzoylmethane (BMDBM) is of no concern as none of the tested animal died after oral application of the extraordinarily high dose of 16000 mg/kg bw. Clinical signs included lethargy and hunched posture. Body weights and gross necropsy were in normal limits.

Acute dermal toxicity was tested up to a dose of 1000 mg/kg bw showing no deaths among test animals. Slight erythema were observed in treated animals but also in the vehicle control, assuming that the vehicle Carbitol has a slight irritant effect to skin.

With an acute oral LD50 > 16000 mg/kg bw no classification applicable for test item BMDBM.

Concerning acute dermal toxicity, the test item was only tested up to a maximum cdose of 1000 mg/kg bw, whereas the regulatory cut-off level for classification according to Regulation (EC) No 1272/2008 (CLP) is 2000 mg/kg bw. However, as several dermal penetration studies (as summarized in section 7.1) have proven that dermal bioavailability of BMDBM is very low and never exceeds 5 %, it can be concluded without reasonable doubt that BMDBM is hardly absorbed through human skin and therefore poses no concern for acute health effects after dermal application. In conclusion, a classification as acute toxic by dermal exposure is not necessary.

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 (EC) No 1272/2008. The LD50 oral was greater than 16000 mg/kg bw and up to 1000 mg/kg bw no dermal effects were observed. As a result the substance is not considered to be classified for acute oral and dermal toxicity under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.