Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP but overall good documentation, comparable to OECD TG 401.

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report date:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Principles of method if other than guideline:
In principle, the methods described in the OECD Guideline 401 were used. Young adult laboratory rats were purchased from breeder. Several groups of 5 rats per sex and dose were treated simultaneously by gavage with preparations of the test substance in suitable vehicle. The concentrations of these preparations were used to achieve comparable volumes per kg body weight. Group-wise documentation of clinical signs was performed over the 14 day study period.
GLP compliance:
no
Remarks:
GLP was not compulsory at the time the study was conducted
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Adipic acid
EC Number:
204-673-3
EC Name:
Adipic acid
Cas Number:
124-04-9
Molecular formula:
C6H10O4
IUPAC Name:
adipic acid
Details on test material:
- Name of test material (as cited in study report): adipic acid
- Physical state: solid
- Analytical purity: 99.8%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: WIGA, Sulzfeld, Germany
- Weight at study initiation:
1470 mg/kg bw dose group: 180 g males, 160 g females
2150 mg/kg bw dose group: 180 g males, 160 g females
3160 mg/kg bw dose group: 190 g males, 170 g females
4640 mg/kg bw dose group: 190 g males, 170 g females
6810 mg/kg bw dose group: 290 g males, 200 g females
10000 mg/kg bw dose group: 270 g males; 180 g females

- Fasting period before study: yes, 16 h prior to application
- Diet: Herlin MRH pellets ad libitum (Company Eggersmann, Rinteln/Weser, Germany)
- Water: ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: 14.7% - 50% suspension in 0.5% carboxymethyl-cellulose
Details on oral exposure:
DOSAGE PREPARATION
- Stock solutions prepared:
14.7% in a 0.5% aqueous carboxymethyl cellulose solution for the 1470 mg/kg bw dose group
21.5% in a 0.5% aqueous carboxymethyl cellulose solution for the 2150 mg/kg bw dose group
31.6% in a 0.5% aqueous carboxymethyl cellulose solution for the 3160 mg/kg bw dose group
46.4% in a 0.5% aqueous carboxymethyl cellulose solution for the 4640 mg/kg bw dose group
50% in a 0.5% aqueous carboxymethyl cellulose solution for the 6810 mg/kg bw dose group
50% in a 0.5% aqueous carboxymethyl cellulose solution for the 10000 mg/kg bw dose group

- Dose volume applied:
10 ml/kg bw of the 14.7% stock solution for the 1470 mg/kg bw dose group
10 ml/kg bw of the 21.5% stock solution for the 2150 mg/kg bw dose group
10 ml/kg bw of the 31.6% stock solution for the 3160 mg/kg bw dose group
10 ml/kg bw of the 46.4% stock solution for the 4640 mg/kg bw dose group
13.62 ml/kg bw of the 50% stock solution for the 6810 mg/kg bw dose group
20 ml/kg bw of the 50% stock solution for the 10000 mg/kg bw dose group
Doses:
1470, 2150, 3160, 4540, 6810, 10000 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
- The animals were observed for mortality and clinical signs of toxicity;
- Frequency of observations: Several times on the application day, thereafter once each working day;
- Body weights were only recorded at the beginning of the study;
- Necropsy of survivors and animals which died performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 560 mg/kg bw
95% CL:
4 650 - 6 770
Mortality:
No mortalities were observed in the 1470 mg/kg bw dose group or the 2150 mg/kg bw dose group. 1 female of the 3160 mg/kg bw dose group and 2 females of the 4640 mg/kg bw dose group died within the first 2 days, while there were no mortalities within the male animals. In the 6810 mg/kg bw dose group all females and 2 of 5 males died within the first two days, in the 10000 mg/kg bw dose group all animals died within 24 h after application (see table 1).
Clinical signs:
1470 mg/kg bw dose group: nothing abnormal observed
2150 mg/kg bw dose group: nothing abnormal observed
3160 mg/kg bw dose group: gasping, apathy, salivation and nose secretion in 1 or 2 animals. Those symptoms disappeared within 24 h.
4640 mg/kg bw dose group: one day after application irregular respiration, apathy, staggering, spastic gait, however the general state of the animals was stated as good; the symptoms of the surviving animals disappeared within 3 days.
6810 mg/kg bw dose group: directly after application and one day later irregular respiration, apathy, lateral or abdominal position, staggering, shaggy fur, spastic gait, bad general state, within 3 days the symptoms had disappeared and the general state of the surviving animals was good
10000 mg/kg bw dose group: directly after application irregular respiration, apathy, staggering, shaggy fur, spastic gait, bad general state
Body weight:
The surviving animals of all groups showed constant body weight gain.
Final body weight:
1470 mg/kg bw dose group: 271 g males, 205 g females
2150 mg/kg bw dose group: 271 g males, 204 g females
3160 mg/kg bw dose group: 276 g males, 200 g females
4640 mg/kg bw dose group: 251 g males, 214 g females
6810 mg/kg bw dose group: 332 g males (females 100% mortality)
10000 mg/kg bw dose group: 100% mortality
Gross pathology:
- Animals which died:
3160 mg/kg bw dose group: brightened liver and kidney; reddened, atonic gut; vessel injection in the gastric mucosa
4640 mg/kg bw dose group: acute dilatation of the heart and acute hyperemia; decay of inner organs
6810 mg/kg bw dose group: acute dilatation of the heart and acute hyperemia, ulceration of the stomach
10000 mg/kg bw dose group: acute dilatation of the heart, ulceration of the stomach, the stomach was atonic, atonic gut
Sacrificed animals: nothing abnormal observed

Any other information on results incl. tables

Dose                compound                sex        mortality 
mg/kg bw)         concentration (%)                (14 days)

10000                50                       m        5/5
                                         f        5/5
6810                 50                       m        2/5
                                         f        5/5
4640                46.4                      m        0/5
                                         f        2/5
3160                31.6                      m        0/5
                                         f        1/5
2150                21.5                      m        0/5
                                         f        0/5
1470                14.7                      m        0/5
                                         f        0/5

Mortality was seen during the first 48 hours. Animals that
died showed acute dilatation of the heart and acute
congestive hypereamia, ulceration of glandular stomach
(bleeding-corrosive gastritis), intestinal atony, reddening
of intestinal mucosa and pale liver. Organs of the survivors were
without findings.

Applicant's summary and conclusion

Executive summary:

In rats, an LD50 value of 5560 mg/kg bw was established in a study similar to OECD TG 401 performed with single doses up to 10 000 mg/kg bw of adipic acid (99.8 %) administered as 50 % suspension in carboxymethyl cellulose vehicle. Mortality was seen during the first 48 hours. Lethal doses caused acute dilatation of the heart and acute congestive hyperaemia, ulceration of glandular stomach (bleeding-corrosive gastritis), pale liver, intestinal atony and reddening of intestinal mucosa. Animals that survived to termination at 14 days showed no gross pathological changes. The doses used in this test were in excess of the currently accepted limit dose

Categories Display