Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1986
Report Date:
1986

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
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): HEXAMETHVLENDIAMIN-RUECKSTAND, HMD-VORLAUF
- Analytical purity: 93.88%
- Impurities (identity and concentrations) > 0.1%: Aminoethylcyclopentylamine 3.57%, Hexamethylenimine 1.35%, Hexylmethylendiamine 0.74%, Pentylmethylendiamine 0.33%, other impurities 0.13%
- pH: 12-13 (10% aqueous solution)

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. Thomae, Biberach, Germany
- Mean weight at study initiation: males 198 g, females 182 g (+- 20%)
- Fasting period before study: 16 h
- Housing: 5 per cage in stainless steel wire mesh cages, Typ DK-III
- Diet (e.g. ad libitum): Kliba-Labordiet, Klingenthalmuehle AG, Kaiseraugst, Switzerland; ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS in fully air-conditioned rooms
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 6.81-21.5% (w/v)

MAXIMUM DOSE VOLUME APPLIED: 10 mL
Doses:
681, 1000, 1470 and 2150 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: observations: several times on the day of administration and at least once each workday; check for moribund and dead animals twice each workday and once on holidays; weighing on day 0, 3, 5, 7 and 13
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 170 mg/kg bw
Based on:
test mat.
95% CL:
1 000 - 1 360
Remarks on result:
other: LD50 of male rats: ca. 1327 mg/kg bw; LD50 of female rats: ca. 1000 mg/kg bw
Mortality:
681 mg/kg bw: 0 males and 0 females died
1000 mg/kg bw: 0 males and 2 females died
1470 mg/kg bw: 4 males and all females died
2150 mg/kg bw: all animals died
All animals that died were dead within 1 day after administration
Clinical signs:
681 mg/kg bw: no clinical signs observed
1000 mg/kg bw: dyspnea, apathy, staggering (only females), piloerection (only females) and poor general state were reversible within one day after administration
1470 mg/kg bw: dyspnea, apathy, abnormal position (only females), staggering, atonia (only females), paresis, piloerection, exsiccosis (only females) and poor general state were reversible in surviving animals within at least one day after administration
2150 mg/kg bw: in addition to the already cited signs, absent pain reflex, absent corneal reflex, narcotic-like state, ophisthotonus and tonic cramps were observed in animals in agony
Body weight:
Mean weights on day 0, 3/5, 7 and 13 in grams
681 mg/kg bw
males: 211 - 225 - 252 - 286
females: 197 - 211 - 226 - 230
1000 mg/kg bw
males: 196 - 220 - 234 - 273
females: 177 - 200 - 208 - 211
1470 mg/kg bw:
males: 189 - 218 - 232 - 262
Gross pathology:
Animals-that died (male and female) :
General congestive hyperemia
Stomach/small intestines: filled with bloody contents
Glandular stomach: diffusely red (gastritis by corrosion)

Sacrificed animals (male and female):
no abnormalities detected.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the applied test condition the test substance has an LD50 value of 1170 mg/kg bw.
Executive summary:

In a study similar to OECD guideline 401, test substance was administered via oral gavage to 5 male and 5 female Wistar rats per dose group (681, 1000, 1470 and 2150 mg/kg bw). The LD 50 value was calculated to be 1170 mg/kg bw. Clinical signs included dyspnea, apathy and poor general state.