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EC number: 205-132-4 | CAS number: 134-20-3
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Acute Toxicity: oral
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:
- guideline study with acceptable restrictions
- Justification for type of information:
- Data is from a NTRL report
Data source
Reference
- Reference Type:
- publication
- Title:
- Acute oral toxicity study of test chemical
- Author:
- NTRL
- Year:
- 1 992
- Bibliographic source:
- U.S. Environmental Protection Agency, NTRL report
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 401 (Acute Oral Toxicity)
- Version / remarks:
- 40 CFR Part 163.81-1.
(ENVIRONMENTAL PROTECTION AGENCY. PESTICIDE PROGRAMS. Proposed Guidelines for Registering Pesticides in the U.S.; Hazard Evaluation:
Humans and Domestic Animals. Acute Oral Toxicity Study.)
- Principles of method if other than guideline:
- To determine to Acute oral toxicity of test chemical in rats.
- GLP compliance:
- not specified
- Test type:
- standard acute method
- Limit test:
- no
Test material
- Reference substance name:
- Methyl o-aminobenzoate
- Cas Number:
- 134-20-3
- Molecular formula:
- C8H9NO2
- IUPAC Name:
- Methyl o-aminobenzoate
- Test material form:
- liquid
- Details on test material:
- IUPAC name: 2-Aminobenzoic acid, methyl ester
Mol. formula: C8H9NO2
Molecular Weight: 151.1641 gm/mol
Smiles: c1(c(cccc1)N)C(OC)=O
InChI: 1S/C8H9NO2/c1-11-8(10)6-4-2-3-5-7(6)9/h2-5H,9H2,1H3
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Rationale for alternative/additional species to rat (if applicable) : No
- Source: Charles River Breeding Laboratories. Inc;Wilmington. Mass
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Rationale for use of males: Not specified
- Age at study initiation: Not specified
- Weight at study initiation:
Males: approx 230-230gm
Females: 180-250 gm
- Fasting period before study: 18 hours
- Housing: Individual in suspended stainless steel
- Historical data: Not specified
- Diet (e.g. ad libitum): Purina Laboratory Chow. ad libitum
- Water (e.g. ad libitum): Elizabethtown water Co. ad libitum
- Acclimation period: Not specified
- Microbiological status when known : no
- Method of randomisation in assigning animals to test and control groups : The animals are randomly selected for each study
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Not specified
- Humidity (%): Not specified
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): Not specified
IN-LIFE DATES: From: To:Not specified
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on oral exposure:
- VEHICLE
- Concentration in vehicle: Not specified
- Amount of vehicle (if gavage):Not specified
- Justification for choice of vehicle:Not specified
- Lot/batch no. (if required): Not specified
- Purity: Not specified
MAXIMUM DOSE VOLUME APPLIED: 5000 mg/kg
DOSAGE PREPARATION (if unusual): Liquids are administered as received.
CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not specified - Doses:
- Single dose: 5.0 g/kg (5000 mg/kg bw)
Range-finding: 0.05, 0.10, 0.50, 1.0 and 2.0 g/kg (50, 100, 500, 1000 and 2000 mg/kg bw)
LD50: 1.2. 1.7. 2.5 and 3.5 g/kg (1200, 1700, 2500 and 3500 mg/kg bw) - No. of animals per sex per dose:
- Total 80 animals (males and females)
Single dose level (5 g/kg): Ten (five/sex)
Range-finding Screen: Ten (one/sex/dose level)
LD50 Determination: Fifty (five/sex/dose level)
Control group: 10 (5 males, 5 females) - Control animals:
- yes
- Details on study design:
- - Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The test animals were observed approximately 1, 2 and 4 hours after dosing, and daily thereafter for fourteen days.
- Necropsy of survivors performed: yes; Gross post mortem examinations were performed on all surviving animals on Day 14 and on all animals which die or were found dead during the study. All abnormalities were recorded but no tissues were saved.
- Clinical signs including body weight: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Body weight: Body weights were checked before fasting, post fasting (prior to dosing) and Terminal: Any animals which do not survive for 14 days were weighed at the time of death or at the time they were found dead.
Results and discussion
- Preliminary study:
- A dose of 5 g/kg was administered initially to 10 animals (5/sex), unless the test substance was suspected to have an LD50 value of less than 5 g/kg.
If no animals die during the fourteen day post-dose observation period, no additional testing is required.
If deaths occur in animals dosed with 5 g/kg, or if the test substance is suspected to have an LD50 which is less than 5 g/kg, the following is done:
A preliminary range-finding screen is performed by administering five different dose levels (usually 0.05. 0.1. 0.5. 1.0 and 2.0 g/kg) to ten rats (one male; one female per dose level). If results do not provide adequate information for selecting doses for the LD50 determination, additional screening studies are performed. Animals were observed for viability for seven days after dosing. Based on the results of this screen, five geometrically spaced dose levels were selected and each dose was administered to ten animals (5/sex) for a determination of the LD50.
Effect levels
- Sex:
- male/female
- Dose descriptor:
- LD50
- Effect level:
- 2 800 mg/kg bw
- Based on:
- test mat.
- 95% CL:
- >= 2 300 - <= 3 300
- Remarks on result:
- other: 50% mortality observed
- Mortality:
- Single dose: All ten animals died after receiving 5 grams/kg of the test material.
Dose range finding: Only one animal died at 2000 mg/kg bw dose level. - Clinical signs:
- other: Some animals in all groups exhibited motor activity decrease, (from the 1 hour interval to Day 7), piloerection (from the 2 hour interval to Day 7). respiratory rate decrease (from the 1 hour interval to Day 2), and ataxia (at the 4 hour interval and on D
- Gross pathology:
- Necropsy observations are presented in table:
- Other findings:
- From Day 8 to termination no abnormalities were recorded for any animals.
Any other information on results incl. tables
Table 1: Dose levels and mortality for the preliminary range-finding study
Dose level (g/kg) |
Mortality |
0.05 |
0/2 |
0.10 |
0/2 |
0.50 |
0/2 |
1.0 |
0/2 |
2.0 |
1/2 |
Table 2: Dose levels, mortality data and LD50 calculations for the LD50 study
Dose level Gm/kg |
Mortality |
||
Male |
Female |
Total |
|
1.2 |
0/5 |
0/5 |
0/10 |
1.7 |
0/5 |
1/5 |
1/10 |
2.5 |
0/5 |
3/5 |
3/10 |
3.5 |
4/5 |
5/5 |
9/10 |
LD50 (gm/kg) |
3.10 |
2.15 |
2.8 |
95% Confidence limits (gm/kg) |
2.60 to 3.50 |
1.55 to 2.75 |
2.3 to 3.3 |
Table 3: Body weights (grams) and day of death; Dose level 1.2 gm/kg
Dose level (g/kg) |
Animal no. and sex |
Pretest weights |
Interim deaths |
Survivors |
||||||
Pre fast |
Post fast |
Terminal weight |
Day of death |
Changea |
Day 7 |
Changea |
Day 14 |
Changea |
||
1.2 |
2504 M |
257 |
228 |
|
|
|
320 |
63 |
372 |
115 |
2510 M |
242 |
216 |
|
|
|
309 |
67 |
355 |
113 |
|
2514 M |
241 |
217 |
|
|
|
283 |
42 |
312 |
71 |
|
2516 M |
250 |
220 |
|
|
|
287 |
37 |
322 |
72 |
|
2525 M |
241 |
219 |
|
|
|
273 |
32 |
308 |
67 |
|
2593 F |
240 |
218 |
|
|
|
266 |
26 |
267 |
27 |
|
2599 F |
227 |
204 |
|
|
|
228 |
1 |
243 |
16 |
|
2604 F |
239 |
216 |
|
|
|
246 |
7 |
256 |
17 |
|
2609 F |
237 |
215 |
|
|
|
249 |
12 |
255 |
18 |
|
2613 F |
236 |
215 |
|
|
|
241 |
5 |
249 |
13 |
aChange from prefasted weight (grams).
Table 4: Body weights (grams) and day of death; Dose level 1.7 gm/kg
Dose level (g/kg) |
Animal no. and sex |
Pretest weights |
Interim deaths |
Survivors |
||||||
Pre fast |
Post fast |
Terminal weight |
Day of death |
Changea |
Day 7 |
Changea |
Day 14 |
Changea |
||
1.7 |
2526M |
232 |
210 |
|
|
|
266 |
34 |
305 |
73 |
2534M |
234 |
210 |
|
|
|
268 |
34 |
310 |
76 |
|
2540M |
230 |
205 |
|
|
|
271 |
41 |
304 |
74 |
|
2541M |
247 |
220 |
|
|
|
306 |
59 |
360 |
113 |
|
2546M |
251 |
220 |
|
|
|
296 |
45 |
340 |
89 |
|
2616F |
238 |
220 |
|
|
|
247 |
9 |
258 |
20 |
|
2619F |
145 |
221 |
|
|
|
266 |
21 |
295 |
50 |
|
2628F |
224 |
205 |
|
|
|
226 |
2 |
259 |
35 |
|
2630F |
231 |
215 |
NR |
Day 2 |
- |
|
|
|
|
|
2595F |
221 |
204 |
|
|
|
239 |
18 |
246 |
25 |
aChange from prefasted weight (grams).
NR: Not recorded
Table 5: Body weights (grams) and day of death; Dose level 2.5 gm/kg
Dose level (g/kg) |
Animal no. and sex |
Pretest weights |
Interim deaths |
Survivors |
||||||
Pre fast |
Post fast |
Terminal weight |
Day of death |
Changea |
Day 7 |
Changea |
Day 14 |
Changea |
||
2.5 |
2512M |
253 |
226 |
|
|
|
303 |
50 |
370 |
117 |
2520M |
236 |
211 |
|
|
|
288 |
52 |
330 |
94 |
|
2523M |
247 |
230 |
|
|
|
287 |
40 |
323 |
76 |
|
2533M |
231 |
210 |
|
|
|
266 |
35 |
305 |
74 |
|
2539M |
249 |
226 |
|
|
|
249 |
0 |
296 |
47 |
|
2600F |
235 |
212 |
|
|
|
229 |
-6 |
245 |
10 |
|
2607F |
230 |
208 |
200 |
Day 1 |
-30 |
|
|
|
|
|
2610F |
250 |
229 |
NR |
Day 2 |
- |
|
|
|
|
|
2615F |
249 |
225 |
|
|
|
254 |
5 |
266 |
17 |
|
2621F |
240 |
224 |
217 |
7 hrs |
-23 |
|
|
|
|
aChange from prefasted weight (grams).
NR: Not recorded
Table 6: Body weights (grams) and day of death; Dose level 3.5 gm/kg
Dose level (g/kg) |
Animal no. and sex |
Pretest weights |
Interim deaths |
Survivors |
||||||
Pre fast |
Post fast |
Terminal weight |
Day of death |
Changea |
Day 7 |
Changea |
Day 14 |
Changea |
||
3.5 |
2545M |
230 |
214 |
200 |
Day 1 |
-30 |
|
|
|
|
2559M |
246 |
220 |
201 |
Day 1 |
-45 |
|
|
|
|
|
2519M |
230 |
205 |
|
|
|
254 |
24 |
298 |
68 |
|
2537M |
246 |
218 |
200 |
Day 1 |
-46 |
|
|
|
|
|
2543M |
248 |
223 |
206 |
Day 1 |
-42 |
|
|
|
|
|
2625F |
241 |
220 |
212 |
Day 1 |
-29 |
|
|
|
|
|
2629F |
235 |
315 |
208 |
Day 1 |
-27 |
|
|
|
|
|
2697F |
234 |
210 |
195 |
Day 1 |
-39 |
|
|
|
|
|
2602F |
219 |
200 |
187 |
Day 1 |
-32 |
|
|
|
|
|
2603F |
247 |
225 |
212 |
Day 1 |
-35 |
|
|
|
|
aChange from prefasted weight (grams).
Table 7: Summary of in-life observations
Dose level (g/kg) |
Observations |
Time interval |
||||||||
Hours |
Days |
|||||||||
1 |
2 |
4 |
1 |
2 |
3 |
4 |
5-7 |
8-14 |
||
1.2 |
Ataxia |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
Red oral discharge |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Respiratory Rate Increase |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Respiratory Rate Decrease |
1 |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Soft Stool |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Piloerection |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
|
Abdominal Griping |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Motor Activity Decrease |
7 |
5 |
1 |
2 |
0 |
0 |
0 |
1 |
0 |
|
1.7 |
Dead |
0 |
0 |
0 |
0 |
1 |
1 |
1 |
1 |
1 |
Ataxia |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Fine Tremors |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Clear oral discharge |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Respiratory Rate Decrease |
0 |
2 |
1 |
4 |
0 |
0 |
0 |
0 |
0 |
|
Piloerection |
0 |
1 |
0 |
4 |
1 |
0 |
1 |
1 |
0 |
|
Motor Activity Increase |
0 |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
|
Motor Activity Decrease |
4 |
4 |
5 |
5 |
4 |
0 |
0 |
0 |
0 |
|
2.5 |
Dead |
0 |
0 |
0 |
2 |
3 |
3 |
3 |
3 |
3 |
Ataxia |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Fine Tremors |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Clear nasal discharge |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Respiratory Rate Decrease |
0 |
3 |
2 |
4 |
0 |
0 |
0 |
0 |
0 |
|
Clear ocular discharge |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Fecal staining |
0 |
0 |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
|
Soft stool |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Piloerection |
0 |
4 |
1 |
3 |
4 |
4 |
0 |
2 |
0 |
|
Motor Activity Increase |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
1 |
0 |
|
Motor Activity Decrease |
5 |
8 |
3 |
6 |
7 |
1 |
1 |
2 |
0 |
|
Prostration |
0 |
0 |
2 |
0 |
0 |
0 |
0 |
0 |
0 |
|
Aggressive |
0 |
0 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
|
3.5 |
Dead |
0 |
0 |
0 |
7 |
9 |
9 |
9 |
9 |
9 |
Ataxia |
0 |
0 |
0 |
2 |
1 |
0 |
0 |
0 |
0 |
|
Fine Tremors |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Clear oral discharge |
2 |
1 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Respiratory Rate Decrease |
2 |
5 |
1 |
2 |
1 |
1 |
0 |
0 |
0 |
|
Clear ocular discharge |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Urinary staining |
0 |
0 |
0 |
1 |
1 |
0 |
0 |
0 |
0 |
|
Piloerection |
0 |
7 |
4 |
2 |
0 |
1 |
0 |
0 |
0 |
|
Abdominal griping |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
|
|
Motor activity decrease |
6 |
9 |
8 |
2 |
1 |
1 |
0 |
0 |
0 |
Prostration |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
0 |
0 |
|
Rales |
1 |
1 |
0 |
0 |
0 |
0 |
0 |
0 |
0 |
Table 8: Day of death and necropsy observations (1.2 gm/kg)
Dose level g/kg |
Animal no. and sex |
Day of death |
Type of deatha |
Observations |
1.2 |
2504 M |
Day 1 |
T |
Lungs: dark red foci, mottled dark red 20%; liver: mottled pale 30%; kidneys: pale; adrenals: pale red. |
2510 M |
Day 14 |
T |
Lungs: dark red foci, mottled dark red 20%; adrenals: dark red. |
|
2514 M |
Day 14 |
T |
Lungs: mottled dark red 80%; kidneys: pale; adrena1s: pale red. |
|
2516 M |
Day 14 |
T |
Lungs: dark red foci; liver: mottled pale 30%; kidneys: mottled pale 60%; adrenals: pale red. |
|
2525 M |
Day 14 |
T |
Lungs: dark red foci; liver: mottled pale 50%; kidneys: mottled pale 40%; adrenals: pale red. |
|
2593 F |
Day 14 |
T |
Lungs: dark red foci; adrenals: dark red foci. |
|
2599 F |
Day 14 |
T |
Lungs: dark red foci, mottled dark red 30%; liver: mottled pale 40%; adrenals: pale red. |
|
2604 F |
Day 14 |
T |
Lungs: dark red foci, mottled dark red 30%; liver: mottled pale 30%; adrenals: pale red. |
|
2609 F |
Day 14 |
T |
Lungs: mottled dark red 60%; liver: mottled pale 30%; adrenals: pale red. |
|
2613 F |
Day 14 |
T |
Lungs: dark red foci; adrenals: dark red foci. |
T= Terminal (Killed on day 14)
Table 9: Day of death and necropsy observations (1.7 gm/kg)
Dose level g/kg |
Animal no. and sex |
Day of death |
Type of deatha |
Observations |
1.7 |
2526M |
Day 1 |
T |
Lungs: dark red foci; adrenals: dark red; mesentary lymph nodes: bright red. |
2534M |
Day 14 |
T |
Lungs: dark red foci; adrenals: pale red. |
|
2540M |
Day 14 |
T |
Lungs: dark red foci, mottled dark red 20%; adrenals: pale red. |
|
2541M |
Day 14 |
T |
Adrenals: dark red foci. |
|
2546M |
Day 14 |
T |
Lungs: dark red foci; mottled pale 10%; kidneys: mottled pale 50%; adrenals: pale red. |
|
2616F |
Day 14 |
T |
Lungs: dark red foci, mottled dark red 20% adrenals: dark red foci. |
|
2619F |
Day 14 |
T |
Lungs: dark red foci; adrenals: pale red. |
|
2628F |
Day 14 |
T |
Lungs: dark red foci, mottled dark red 60%; adrenals: pale red. |
|
2630F |
Day 2 |
F |
Clear oral discharge; lungs: pale, tan patches 50%; liver: mottled tan; stomach: contains dark brown fluid; intestines: contain brown fluid; kidneys: tan; adrenals: dark red; urinary bladder: contains brown fluid. |
|
2595F |
Day 14 |
T |
Lungs: dark red foci. |
T= Terminal (Killed on day 14)
F=Found dead (Day given is day found dead).
Table 10: Day of death and necropsy observations (2.5 gm/kg)
Dose level g/kg |
Animal no. and sex |
Day of death |
Type of deatha |
Observations |
2.5 |
2512M |
Day 14 |
T |
Lungs: dark red foci; liver: mottled pale 40%; kidneys: mottled pale 30%; adrenals: pale red. |
2520M |
Day 14 |
T |
Lungs: dark red foci; liver: mottled pale 40%; kidneys: mottled pale 20%; adrenals: pale red. |
|
2523M |
Day 14 |
T |
Lungs: dark red foci, mottled dark red 30%; liver: anterior edges clear; kidneys: mottled pale 60%; adrenals: pale red. |
|
2533M |
Day 14 |
T |
Lungs: dark red foci; liver: mottled pale 40%; kidneys: mottled pale 50%; adrenals: pale red. |
|
2539M |
Day 14 |
T |
Lungs: dark red foci; kidneys: mottled pale 70%; adrenals: pale red. |
|
2600F |
Day 14 |
T |
Lungs: dark red foci; liver: mottled pale 20%; adrenals: pale red. |
|
2607F |
Day 1 |
F |
Brain: blood vessels injected; lungs: mottled dark red and pale 70%; stomach: contains thick tan material; intestines: contain reddish yellow viscous fluid; kidneys: pale; adrenals: dark red. |
|
2610F |
Day 2 |
F |
Clear oral discharge; clear nasal discharge; yellow urinary staining; lungs: pale red; liver: mottled tan, dark red foci; intestines: contain dark red-black fluid; spleen: diminished, black wrinkled; kidneys: tan; adrenals: dark red. |
|
2615F |
Day 14 |
T |
Lungs: dark red foci; adrenals: pale red. |
|
2621F |
7 hours |
F |
Stomach: contains tan fluid; jujunum: contains reddish yellow fluid; duodenum: contains tan fluid; adrenals: dark red. |
T= Terminal (Killed on day 14)
F=Found dead (Day given is day found dead).
Table 11: Day of death and necropsy observations (3.5 gm/kg)
Dose level g/kg |
Animal no. and sex |
Day of death |
Type of deatha |
Observations |
3.5 |
2545M |
Day 1 |
F |
Brain: blood vessels injected; stomach: pyloric region - reddish tint, pronounced vascularization, contains thick tan material; intestines: appeared reddened, contain reddish yellow fluid; kidneys: pale; adrenals: dark red. |
2559M |
Day 1 |
F |
Brain: blood vessels injected; lungs: wrinkled; stomach: contains thick grey green material; intestines: vascu1arized, contains thick brown fluid; spleen: extremely diminished; kidneys: mottled pale 30%; adrenals: dark red. |
|
2519M |
Day 14 |
T |
Adrenals: pale red |
|
2537M |
Day 1 |
F |
Clear oral discharge; red nasal discharge; brain: blood vessels injected; lungs: dark red foci; mottled dark red 20%; stomach: pyloric region - vascularized, contains thick tan substance; intestines: vascularized, contain red fluid; adrenals: pale red; testes: undescended. |
|
2543M |
Day 1 |
F |
Fecal staining; brain: blood vessels injected; left lung; mottled black; liver: mottled pale, clear edges; stomach: distended with gas, contains grey green fluid; intestines: pronounced vascularization, contain thin brown fluid; spleen: diminished; adrenals: extremely dark red. |
|
2625F |
Day 1 |
F |
Brain: blood vessels injected; lungs: dark red foci; liver: clear edges; stomach: pyloric region - reddish tint, contains thick tan material; intestines: contain reddish yellow viscous fluid; kidneys: pale; adrenals: pale red. |
|
2629F |
Day 1 |
F |
Lungs: mottled tan 50%; liver: clear edges; stomach: distended with gas, contains viscous tan substance; kidneys: mottled pale 50%; adrenals: dark red. |
|
2697F |
Day 1 |
F |
Clear oral discharge; lungs: mottled dark red 30%; liver: mottled pale 30%; stomach: distended with yellow tan fluid; intestines: contain yellow tan fluid; spleen: roughened; kidneys: pale; adrenals: pale red. |
|
2602F |
Day 1 |
F |
Brain: blood vessels injected; lungs: mottled dark red 30%, dark red foci; liver: clear edges; stomach: distended with gas, contains thick tan material and black material; intestines: black material in duodenum; kidneys: pale; adrenals: dark red. |
|
2603F |
Day 1 |
F |
Lungs: dark red foci 100%; stomach: contains viscous tan material; intestines: contains reddish yellow fluid; kidneys: mottled pale 40%; adrenals: pale red. |
T= Terminal (Killed on day 14)
F=Found dead (Day given is day found dead).
Table 12: Body weights (grams) of Control group
Animal no. |
Sex |
Pre fast |
Post fast |
Day 7 |
Changea |
Day 14 |
Changea |
2509 |
M |
259 |
230 |
318 |
59 |
350 |
91 |
2527 |
M |
250 |
221 |
290 |
40 |
317 |
67 |
2549 |
M |
251 |
227 |
310 |
59 |
350 |
99 |
2554 |
M |
252 |
222 |
315 |
63 |
352 |
100 |
2556 |
M |
251 |
225 |
297 |
46 |
322 |
71 |
2571 |
F |
235 |
212 |
253 |
18 |
264 |
29 |
2577 |
F |
238 |
217 |
253 |
15 |
278 |
40 |
2581 |
F |
254 |
228 |
262 |
8 |
280 |
26 |
2584 |
F |
233 |
210 |
249 |
16 |
242 |
9 |
2588 |
F |
210 |
201 |
230 |
20 |
255 |
45 |
aChange from initial (prefasted) weight.
Table 13: NECROPSY OBSERVATIONS - CONTROL ANIMALS (TERMINAL - DAY 14)
Animal no. |
Sex |
Observations |
2509 |
M |
Kidneys: mottled pale 30%; adrenals: dark red foci |
2527 |
M |
Lungs: dark red foci throughout; liver: mottled pale 20%; kidneys: mottled pale 50%; adrenals: dark red. |
2549 |
M |
Lungs: dark red foci; adrenals: pale red |
2554 |
M |
Lungs: dark red foci; kidneys: mottled pale 70%; adrenals: dark red foci. |
2556 |
M |
Lungs: dark red foci throughout; liver: mottled pale 60%; kidneys: pale; adrena1s: pale red. |
2571 |
F |
Lungs: dark red foci throughout; adrenals: dark red foci. |
2577 |
F |
Adrenals: pale red. |
2581 |
F |
Kidneys: mottled pale 50%; adrenals: pale red |
2584 |
F |
Lungs: mottled dark red 40%; adrenals: pale red |
2588 |
F |
Lungs: mottled bright red 30%; adrenals: pale red. |
Applicant's summary and conclusion
- Interpretation of results:
- other: Not classified
- Conclusions:
- Acute oral toxicity study was carried out on rats to determine the toxic nature of test chemical.50% mortality was observed at a dose level of 2800 mg/kg bw with 95% confidence limit of 2300 to 3300 mg/kg bw. Thus, the LD50 value was >2000 mg/kg bw indicating that the test chemical is not toxic to rats when administered orally and can be classified under the category ‘Not classified’.
- Executive summary:
Acute oral toxicity study was carried out on rats to determine the toxic nature of test chemical. A total of 80 Male and female Sprague-Dawley rats were used during the study. The test chemical was administered orally by gavage at various dose ranges for 14 days. The study was carried out in three different stages; Single dose study, a dose of 5 g/kg is administered initially to 10 animals (5/sex), unless the test substance is suspected to have an LD50 value of less than 5 g/kg. If no animals die during the fourteen day post-dose observation period, no additional testing is required; Range finding study, If deaths occur in animals dosed with 5 g/kg, or if the test substance is suspected to have an LD50 which is less than 5 g/kg, the following is done: A preliminary range-finding screen is performed by administering five different dose levels (usually 50, 100, 500, 1000 and 2000 mg/kg) to ten rats (one male; one female per dose level). If results do not provide adequate information for selecting doses for the LD50 determination, additional screening studies are performed; and LD50 determination study, animals were observed for viability for seven days after dosing. Based on the results of this screen, four geometrically spaced dose levels ie. 1200, 1700, 2500 and 3500 mg/kg bw were administered and each dose was administered to ten animals (5/sex) for a determination of the LD50. The test chemical was administered by oral intubation, using a ball-tipped intubation needle. Doses were calculated using pre-fasted body weights. Whenever possible, a constant concentration of test substance was administered at all doses (i.e., varying doses were achieved by varying the volume of the dosing mixture) 60 ml of test substance per kg of body weight was considered the maximum volume which can be administered to a rat; doses in excess of this amount were not administered. In order to provide control data, ten animals (5/sex) were dosed with methylcellulose in a volume of 45.0 ml/kg [Because maximum dose specified in protocol (60 ml/kg) was found to be excessive, dose was reduced to 45 ml/kg]. Mortality data, in-life observations (14 days) and necropsy observations for these animals are tabulated. The test animals were observed approximately 1, 2 and 4 hours after dosing, and daily thereafter for fourteen days. Gross post mortem examinations were performed on all surviving animals on Day 14 and on all animals which die or were found dead during the study. All abnormalities were recorded but no tissues were saved. Body weights were checked before fasting, post fasting (prior to dosing) and Terminal; any animals which do not survive for 14 days were weighed at the time of death or at the time they were found dead. Mortality was observed in all animals at dose level of 5000 mg/kg bw and only one animal died at 2000 mg/kg bw dose in range finding study. Some animals in all groups exhibited motor activity decrease, (from the 1 hour interval to Day 7), piloerection (from the 2 hour interval to Day 7), respiratory rate decrease (from the 1 hour interval to Day 2), and ataxia (at the 4 hour interval and on Days 1 and 2). All surviving animals exhibited body weight gains at Day 14, the majority of animals exhibited body weight gains at Day 7, except for one animal which exhibited a slight weight loss and one animal which showed no change. Animals dying prior to termination exhibited weight losses. From Day 8 to termination no abnormalities were recorded for any animals. 50% mortality was observed at a dose level of 2800 mg/kg bw with 95% confidence limit of 2300 to 3300 mg/kg bw. Thus, the LD50 value was >2000 mg/kg bw indicating that the test chemical is not toxic to rats when administered orally and can be classified under the category ‘Not classified’.
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