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Description of key information

Oral: 
- acute toxicity, oral, rat, Wistar, OECD 401 (limit test), Read across to CAS 1116-76-3: LD50>= (female/male) 2000 mg/kg bw, one death male and one death female
Dermal:
- acute toxicity, dermal, rat, Wistar, OECD 402, dermal discriminating dose-value (female/male) 5000mg/kg bw
Inhalation:
- No information on acute inhalation available for Amines, tri-C8-10-alkyl.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to OECD guideline study, with acceptable restrictions (no data on test substance purity, limited documentation)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(adopted 1987)
Deviations:
yes
Remarks:
(limited documentation)
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GMBH, D-7950 Biberach, Germany
- Age at study initiation: no data
- Weight at study initiation: anmals of comparable weight ( ± 20% of the mean weight)
mean weight: males 191 g; females 181 g
- Fasting period before study: 16 hrs before administration of the test substance
- Housing: 5 animals per cage, in stainless steel wire mesh cages, Type DK-III
- Diet (ad libitum): Kliba-Labordiaet 343, Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland
- Water (ad libitum): tap water
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 40 g/100 mL
- Amount of vehicle (if gavage): 5 mL/kg bw
- Justification for choice of vehicle: The test substance is insoluble in water.

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg bw

Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 animals/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
Recording of signs and symptoms were performed several times on the day of administration, then at least once each workday. A check for moribund and dead animals was performed twice each workday and once on holidays.
Body weights of individual animals were recorded before test start. After 7 and 13 days, group-wise documentation of body weights was performed.

- Necropsy of survivors performed: yes
Food was withdrawn about 16 hrs before sacrifice with CO2. Then, necropsy with gross-pathological examination was performed. Necropsy of all animals that died during the study, was conducted as early as possible.

- Other examinations performed: clinical signs, body weight: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
On day 7 one male rat out of five and one female rat out of five rats treated with 2000 mg/kg bw of the test substance died. The remaining animals survived until the end of the observation period (14 days after administration). 20 % mortality was observed during the present study.
Clinical signs:
Male animals:
- no abnormalities

Female animals:
- from day 5 until day 6: dyspnoea, apathy and poor general state
- from day 5 until day 7: spastic gait and piloerection
- on day 7: impaired general state
Body weight:
Male animals:
Body weights of the male rats increased within the normal range throughout the study period (249 g after 7d, 283 g after 13 d).

Female animals:
Body weights of the female rats did not increase during the first study week, but decreased slightly (179 g), then started to increase during the second week (199 g).
Gross pathology:
Deceased animals: general congestion.

Sacrificed animals: no pathologic findings noted.

Mean body weights:

 

Mean body weights [g]

After x days [d]

males

females

0

191

181

7

249

179

13

283

199

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted to current guidelines under GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
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:Young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation:Animals of comparable weight (± 20% of the mean weight) 201-252g
- Fasting period before study:
- Housing:housed in fully air-conditioned rooms, Makrolon cage, type III, Single housing
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22°C +- 3°C
- Humidity (%):30 – 70%
- Air changes (per hr):Approx. 10
- Photoperiod (hrs dark / hrs light):12 h / 12 h
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure:40 cm² (corresponds to at least 10% of the body surface)
- % coverage:10 %

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

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 6.26 ml/kg bw
- Constant volume or concentration used: no, depends on bw.
Duration of exposure:
24h
Doses:
5000mg/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:
- Body weight determination:
-- Individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation.
- Clinical observations:
-- Recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals.
Scoring of skin findings: Individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), several times (see results) until the last day of observation.
- Mortality:
-- A check for any dead or moribund animals was made at least once each workday, these records are archived by Bioassay.
- Pathology:
-- Necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time.
Necropsy of survivors performed: yes
- Other examinations performed: assessment of skin reaction
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred
Clinical signs:
No signs of systemic toxicity effects were observed
Body weight:
Mean body weight of the animals decreased during the first post-exposure observation week, probably due to the severe skin reaction, but increased (only slightly in females) during the second week.
Gross pathology:
No macroscopic pathologic abnormalities were noted
Other findings:
The following test item-related local effects were recorded during the course of the study:
Well-defined to severe erythema (grade 2 to 4)
Very slight to severe edema (grade 1 to 4)
Incrustations
Additionally, the local clinical signs were noted beyond the application site.
Interpretation of results:
not classified
Remarks:
Migrated information EU GHS Criteria used for interpretation of results: other:
Conclusions:
The acute dermal median lethal dose (LD50) of Amines, tri-C8-10-alkyl was determined to be LD50, dermal, rat > 5000 mg/kg bw
Executive summary:

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 5000 mg/kg bw of the undiluted test itemAmines, tri-C8-10-alkyl to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours. The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days.

 

  • No mortality occurred.

  • No signs of systemic toxicity effects were observed

 

  • The following test item-related local effects were recorded during the course of the study:

 

o  Well-defined to severe erythema (grade 2 to 4)

o  Very slight to severe edema (grade 1 to 4)

o  Incrustations

o  Additionally, the local clinical signswere noted beyond the application site.

 

  • Mean body weight of the animals decreased during the first post-exposure observation week, probably due to the severe skin reaction, but increased (only slightly in females) during the second week.

 

  • 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 > 5000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
5 000 mg/kg bw

Additional information

There are valid study data available assessing the actue dermal toxicity of Amines, tri-C8-10-alkyl.

No valid study are data available assessing the acute oral toxicity of Amines, tri-C8-10-alkyl. Nevertheless there are information from a “semi” read across substance Amines, tri C8 alkyl (CAS 1116-76-3) containing only C8 C-chains. As the substance registered here contains also C8 chain but partly C10 chains the structure are assumed to very similar and partly the same. Therefore the suitability of a read across to the pure C8 chain alkyl amine is assumed and comparable toxicological behaviour is expected. As both structures are that similar no further separate analogue document is created.

No valid information for Amines, tri-C8-10-alkyl on inhalation toxicity is available.

Dermal:

OECD conform studies:

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 5000 mg/kg bw of the undiluted test item Amines, tri-C8-10-alkyl to the clipped skin (dorsal and dorso-lateral parts of the trunk) and covered by semi-occlusive dressing for 24 hours according to OECD guideline 402 (BASF SE, 2013, 11A0674/12X343). The application area comprised at least 10% of the total body surface area. The animals were observed for 14 days. No mortality occurred and no signs of systemic toxicity effects were observed. The following test item-related local effects were recorded during the course of the study:  Well-defined to severe erythema (grade 2 to 4),  very slight to severe edema (grade 1 to 4), incrustations and additionally, the local clinical signs were noted beyond the application site.Further the mean body weight of the animals decreased during the first post-exposure observation week, probably due to the severe skin reaction, but increased (only slightly in females) during the second week, but 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 > 5000 mg/kg bw

 

Information for structural very similar substances [Tri-N-Octylamine (CAS1116-76-3)]:

Oral:

OECD conform studies:

An acute oral toxicity study was conducted following a study protocol comparable to OECD guideline No. 401 (limit test) was performed with Tri-N-Octylamine (CAS1116-76-3) (BASFSE, 1988, 10A0264/881077). Five male and five female Wistar rats were administered 2000 mg/kg bw test substance by gavage and observed for clinical signs of intoxication during the 14 days observation period.One male out of five rats and one female out of five rats, respectively, died on day 7 of the study. The other animals survived until the end of the observation period. While the male animals did not show any clinical signs of toxicity, the female rats showed dyspnoea, poor general state, spastic gait, piloerection and apathy. Necropsy revealed general congestion in the deceased animals and no abnormalities in the animals sacrificed at study termination.Under the conditions of the present study, the LD50 was determined to be greater than 2000 mg/kg bw.

 

Assessment of acute toxicity:

Oral: There is no study available investigating the acute oral toxicity of Amines, tri-C8-10-alkyl, nevertheless there are information available about acute toxicity from a strongly structural related substanceTri-N-Octylamine (CAS1116-76-3). The animal study shows only slight signs of toxicity, LD50>= (female/male) 2000 mg/kg bw (one male and one female died), there a low toxicity is also assumed for the close homologe Amines, tri-C8-10-alkyl. Hence a very low acute oral toxicity is assumed and no classification is derived.

Dermal: The information available for the available acute dermal toxicity study points to very low dermal toxicity. The discriminating dose (no mortality but Well-defined to severe erythema/edema and incrustration) determined is 5000 mg/kg. Therefore a very low acute dermal toxicity is assumed and no classification is derived.

Inhalation: No acute inhalation study available is available. This study was not proposed or conducted because exposure consideration point to a more likely dermal and oral exposure and according to the REACH Regulation (EC) No 1907/2006, Annex VIII, 8.5 only information on two application routes needs to be provided, with test item administration via the most appropriate route.

Key study assignment:

As there is only one relevant and reliable study available assessing each the oral and the dermal toxicity and both were well performed and documented according to OECD guidelines and under GLP, these study were therefore included as key studies.

No acute inhalation study available.


Justification for selection of acute toxicity – oral endpoint
most reliable and relevant available result

Justification for selection of acute toxicity – dermal endpoint
most reliable and relevant available result

Justification for classification or non-classification

Based on the available results above,no classification and labelling is required according to Regulation No (EC) 1272/2008 (CLP) or Directive 67/548/EEC (DSD) criteria.

Labelling for acute toxicity:

GHS: no classification

DSD: no classification

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