Registration Dossier

Administrative data

Description of key information

Acute oral toxicity

LD50 (rat, combined) = 10066 mg/kg bw (read-across from 1,4-BDDMA); OECD Guideline 401; pre-GLP study

LD50 (rat) = 5762 mg/kg bw pre-GLP/ pre-guideline study
Acute inhalation toxicity: no relevant route of exposure
Acute dermal toxicity: LD50 (rabbit) > 3000 mg/kg bw ; no detailed information on method

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
Study performed before implementa tion of GLP
Justification for type of information:
Read across to the analogous substance.
REPORTING FORMAT FOR THE ANALOGUE APPROACH
see attached category document

1. HYPOTHESIS FOR THE ANALOGUE APPROACH
see attached category document, chapter 1.1ff

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
see attached category document, chapter 1

3. ANALOGUE APPROACH JUSTIFICATION
see attached category document, chapter 5 (Toxikokinetics) and endpoint specific chapters

4. DATA MATRIX
see attached category document, table in chapter 1.2 and endpoint specific chapters
Reason / purpose for cross-reference:
read-across source
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Appraisal of the safety of chemicals in foods, drugs and cosmetics, by the Staft of the Division of Pharmacology, US FDA (1959)
Principles of method if other than guideline:
Study performed before implementation of the corresponding guideline, but performance complies to a large extent to the later implemented international guideline.
GLP compliance:
no
Remarks:
Study performed before implementation of GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: no data
- Weight at study initiation: 160 – 240 g
- Fasting period before study: 16 h before study initiation
- Housing:individually
- Diet (e.g. ad libitum): laboratory rodents standard diet, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 45 – 55%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 12.60 mL/kg bw
Doses:
7.94, 8.97, 10.00, 11.30, 12.60 mL/kg bw corresponding to 8131, 9185, 10240, 11571 and 12902 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing day 0, day 14; clinical signs 20 min, 1 h, 3 h, 24 h, 7 d 14 d post application
- Necropsy of survivors performed: yes
Statistics:
LD50-calculation by probit analysis
Sex:
male/female
Dose descriptor:
LD50
Effect level:
10.066 mg/kg bw
Based on:
test mat.
95% CL:
9 400 - 10 035
Sex:
male/female
Dose descriptor:
LD50
Effect level:
9.83 mL/kg bw
Based on:
test mat.
95% CL:
9.18 - 10.47
Mortality:
- 7.94 mL/kg bw dose group: 1/5 males, 2/5 females died
- 8.97 mL/kg bw dose group: 2/5 males, 2/5 females died
- 10.00 mL/kg bw dose group: 3/5 males, 2/5 females died
- 11.30 mL/kg bw dose group: 3/5 males, 3/5 females died
- 12.60 mL/kg bw dose group: 4/5 males, 4/5 females died
animals died within 3 days p.a.
Clinical signs:
- reduced activity, piloerection and ataxia starting 1 to 3 hours after application, lasting for 24 hours; in the highest dose group lasting for 7 days
Body weight:
- body weight gain of surviving animals was similar in all dose groups
Gross pathology:
- redness of stomach and intestinal mucosa in died and surviving animals
Other findings:
n/a
Interpretation of results:
GHS criteria not met
Conclusions:
On the basis of the results obtained after a single oral administration, the oral LD50 was determined to be 9.83 mL/kg bw corresponding to 10.06 g/kg bw referring to 100 % active substance (based on a density of 1.024 g/cm³).
Executive summary:

In an acute oral toxicity study similar to OECD guideline 401, groups of fasted Wistar rats (5 males + 5 females) were given a single oral dose of undiluted 1,4-BDDMA (according to supplier's information: purity ca. 90%, reactive ester content of 98 %) at doses of 7.94, 8.97, 10.00, 11.30 and 12.60 mL/kg (corresponding to 8131, 9185, 10240, 11571 and 12902 mg/kg bw based on a density of 1.024 g/cm³) and observed for 14 days.

  

The following mortality was observed: 1 male and 2 females in the 7.94 mL/kg dose group, 2 males and 2 females at 8.97 mL/kg, 3 males and 2 females at 10.00 mL/kg, 3 males and 3 females at 11.30 mL/kg, 4 males and 4 females at 12.60 mL/kg. The surviving animals showed reduced activity, piloerection and ataxia starting 1 to 3 hours after application and lasting for 24 hours; in the highest dose group the symptoms lasted up to 7 days. No changes in body weight gain were observed in the surviving animals throughout all dose groups. At necropsy redness of stomach and intestinal mucosa in died and surviving animals was observed.

Oral LD50 Combined = 9.83 mL/kg bw (95% c.i. 9.18 - 10.47 mL/kg bw) corresponding to 10.06 g/kg bw

NOTE: Any of data in this dataset are disseminated by the European Union on a right-to-know basis and this is not a publication in the same sense as a book or an article in a journal. The right of ownership in any part of this information is reserved by the data owner(s). The use of this information for any other, e.g. commercial purpose is strictly reserved to the data owners and those persons or legal entities having paid the respective access fee for the intended purpose.

Endpoint:
acute toxicity: oral
Type of information:
not specified
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
limited details available
GLP compliance:
not specified
Species:
rat
Sex:
not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
5 762 mg/kg bw
Based on:
not specified
Remarks on result:
other: 5.7 ml/kg (calculated) = 5762 mg/kg (density 1.011 g/cm³)

Original value: 5.7 ml/kg (calculated LD50)

Interpretation of results:
GHS criteria not met
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
10 066 mg/kg bw
Quality of whole database:
One relevant, reliable (Klimisch score = 2) and adequate study is available.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
3 000 mg/kg bw
Quality of whole database:
One relevant, reliable (Klimisch score = 2) and adequate publication (peer-reviewed handbook data, pre-guideline study) is available.

Additional information

Reliable (RL2), relevant and adequate data are available for the acute oral toxicity of the closely related isomer 1,4-BDDMA, which is used for read-across and the dermal toxicity of 1,3-BDDMA.

 

Acute oral toxicity

In an acute oral toxicity study similar to OECD guideline 401, groups of fasted Wistar rats (5 males + 5 females) were given a single oral dose of undiluted 1,4-BDDMA according to supplier's information: purity ca. 90%, reactive ester content of 98 %)at doses of 7.94, 8.97, 10.00, 11.30 and 12.60 mL/kg (corresponding to 8131, 9185, 10240, 11571 and 12902 mg/kg bw based on a density of 1.024 g/cm³)and observed for 14 days (Röhm 1978).

The following mortality was observed: 1 male and 2 females in the 7.94 mL/kg dose group, 2 males and 2 females at 8.97 mL/kg, 3 males and 2 females at 10.00 mL/kg, 3 males and 3 females at 11.30 mL/kg, 4 males and 4 females at 12.60 mL/kg. The surviving animals showed reduced activity, piloerection and ataxia starting 1 to 3 hours after application and lasting for 24 hours; in the highest dose group the symptoms lasted up to 7 days. No changes in body weight gain were observed in the surviving animals throughout all dose groups. At necropsy redness of stomach and intestinal mucosa in died and surviving animals was observed.

Oral LD50 (rat) Combined = 9.83 mL/kg bw (95% c.i. 9.18 - 10.47 mL/kg bw) corresponding to 10.06 g/kg bw.

This study result from the analogous substance 1,4 -BDDMA confirms to the result of an older study in rats done with 1,3 -BDDMA itself (Lawrence 1974). Due to the limited available data, the reliability is rated with Klimisch 4. In this study, the acute oral LD50 was found to be 5762 mg/kg bw in rats.

 

Acute inhalative toxicity

A study on acute inhalation toxicity is unjustified in accordance to REACH regulation Annex VIII, column 2 due to exposure considerations as well as in accordance to REACH regulation Annex XI due to scientific considerations. The substance has a low vapour pressure. The use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur. Furthermore, systemic toxicity relevant to humans did not appear in acute by oral or dermal exposure. Considering the exposure probability and the available information on the intrinsic toxic activity of the substance, an inhalative systemic toxicity risk to humans is unlikely and therefore, the conduct of an inhalative toxicity study is not scientifically necessary. Thus, also animal welfare is respected according to REACH intentions.

Acute dermal toxicity

The acute dermal LD50 of 1,3-BDDMA is reported to be >3000 mg/kg bw in rabbit in a screening study, whose reliability is rated with Klimisch 2 (peer-reviewed handbook data).

Based on the low systemic toxicity after acute oral administration and the calculated low dermal absorption potential (Heylings 2013, see chapter Toxicokinetics), no classification according UN-GHS is warranted.

 

Based on the available information, the acute toxicity of 1,3-BDDMA is low for oral and dermal routes of administration in rat and rabbits. There are no data gaps in acute toxicity. Even though there is no information on acute inhalative toxicity, there is no reason to believe that the acute toxicity is higher for this route of exposure. Even though there is no information on acute toxicity in humans, there is no reason to believe that the low acute toxicity observed in experimental animals would not be relevant for human health.


Justification for selection of acute toxicity – oral endpoint
pre-guideline study similar to OECD guideline, pre-GLP; read across from the analogous substance 1,4 -BDDMA (read across justified in the category document)

Justification for selection of acute toxicity – inhalation endpoint
Inhalation is no relevant route of exposure and testing by inhalation is not appropriate. Exposure of humans via inhalation is unlikely taking into account the low vapour pressure and the low possibility of exposure to aerosols, particles or droplets of an inhalable size.

Justification for selection of acute toxicity – dermal endpoint
pre-guideline study, pre-GLP, peer-reviewed handbook data

Compliance to REACh requirements

The acute oral requirement is covered with a reliable rat study from the analogous substance 1,4-BDDMA and a low reliability oral rat study, performed with the substance itself. The acute dermal requirement is covered with and an reliable acute dermal study in rabbits, performed with the substance itself. An acute inhalation study is waived for exposure reasons (low vapour pressure).

Justification for classification or non-classification

Based on the available data, 1,3-BDDMA does not need to be classified for acute toxicity according to regulation (EC) 1272/2008 or UN-GHS. Thus, no labelling is required.