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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study according to guideline study, no GLP study (GLP was not mandatory when study was done)

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1982
Report Date:
1982
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
(1981-5-12)
Deviations:
no
GLP compliance:
no
Remarks:
GLP was not mandatory when study was done
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): N,N,N',N'-Tetramethyl-1,6-hexanediamine
- Analytical purity: 97.5 %
- Lot/batch No.: no data
- Impurities (identity and concentrations): N,N',N'-Trimethyl-1,6-hexanediamine 2%
- Expiration date of the lot/batch: december 1983

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: 12 weeks
- Weight at study initiation (mean weight): 180 g± 20% (male animals): 190 ± 20% (female animals)
- Fasting period before study: 16 hrs before study begin
- Housing: 5 animals per cage (type DK-III stainless steel wire mesh cages, supplied by Becker & Co., Castrop-Rauxel, Germany)
- Diet: SSNIFF R; Ssniff Versuchstierdiaeten, Soest, Germany
- Water: fully demineralized water ad libitum each workday, tap water ad libitum on public holidays
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20- 26
- Humidity (%): 45- 75
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4.64% (dose: 464 mg/kg bw), 3.16% (dose: 316 mg/kg bw:), 2.15% (dose: 215 mg/kg bw)
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: aqueous preparation corresponding to the physiological medium

Doses:
215, 316, 464 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 of weighing: signs and symptoms were recorded immediately after substance application (< 15min) after 15 min, 30 min, 1hr, 2, 4, 5 hrs. Afterwards once per workday. Check for moribund and dead animals twice each workday and once daily at weekends on public holidays. Weighing was done after beginning of the test and after 4, 7, 13 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 316 - < 464 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 5 males died at the highest dose (464 mg/ kg bw) (1 day after dosing) ; 5 females died at highest dose (1 day after dosing) , 1 female died 1 day at the middle dose (1 day after dosing)
Sex:
male
Dose descriptor:
LD50
Effect level:
> 316 - < 464 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 5 males died at the highest dose (464 mg/ kg bw) (1 d after dosing.)
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 350 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 5 females died at highest dose (1 day after dosing) , 1 female died 1 day after dosing at the middle dose level
Mortality:
at high dose (464 mg/kg bw): 5/5 males (after 1 d) and 5/5 females (after 1d) died
at medium dose (316 mg/kg bw): 0/5 males 1/5 females (after 1d) died
at low dose (215 mg/kg bw): 0/5 males and 0/5 females died
Clinical signs:
following symptoms were seen in males:
all doses:
dyspnea , apathy, staggering, spastic gait, piloerection, poor general state (from ca. 15 min to day 1)
at highest dose (464 mg/kg bw): cyanosis (after 4 hrs) and exsiccosis (after 30 min)

following symptoms were seen in females:
all doses:
dyspnea , apathy, staggering, spastic gait, piloerection, poor general state (low and medium dose: from about 15 min to day 1; high dose : from about 15 min to mortality )

at highest dose (464 mg/kg bw): cyanosis and exsiccosis were seen
Body weight:
normal bodyweight gain during study for all surviving animals in low and medium dose (at highest dose all animals died after 1 day)
Gross pathology:
Animals that died (males and females):
Lungs: moderate to severe emphysema; stomach: diffuse redness of the glandular stomach; individual animals with extensive hemorrhagic gastritis; stomach: blood colored contents

Sacrificed animals (males and females):
Stomach: mucosa of the glandular stomach thickened and massive convolution

Any other information on results incl. tables

Table 1: Mortality of male and female animals

Dose [mg/kg bw]

Toxicological
results*

mortality

Males

215

0/5

0%

316

0/5

0%

464

5/5

100%

 

 

 

Females

215

0/5

0%

316

1/5

20%

464

5/5

100%

LD50 = 316- 464 mg/kg bw

* first number = number of dead animals
second number = number of animals used

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on an acute oral LD50 value of 316-464 mg/kg bw, the substance is classified in Category 4 under CLP.
Executive summary:

A test for determination of the acute oral of toxicity for N,N,N',N'-tetramethylhexane-1,6-diamine was conducted on 5 male and 5 female Wistar rats. The study was done according to the OECD guideline 401. Following doses were tested: 215, 316 and 464 mg/kg bw. At the lowest dose level no animals died, at the medium dose level 1/5 female rats and at the highest dose level all animals died. Therefore an LD50 value in the range of 316 to 464 mg/kg bw was determined.