Neodecanoic acid, iron salt

Endpoint summary

Description of key information

For the oral route, suitable test data is available for the target substance Neodecanoic acid, iron salt. In an acute oral toxicity study conducted according to OECD 420, one animal treated at 2000 mg/kg bw was humanely killed approximately 3 hours after dosing due the severity of the clinical signs. A further four female rats received as a second step a single oral dose of 300 mg/kg bw. No deaths were noted in animals treated at 300 mg/kg bw. Therefore, the LD50 is >300 and < 2000 mg/kg bw.

For the dermal and inhalation route, no acute toxicity data from studies conducted with the target substance are available. Thus, data from suitable read-across partners were used. For details and justification of read-across please refer to the report attached in section 13 of IUCLID. Read-across substances did not shown any acute toxicity via dermal or inhalation route.

In conclusion, based on the available data, the target substance is not acutely toxic via the dermal and inhalation route, but classification as Acute Tox. 4, H302 for the oral route is warranted.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017-09-04 to 2017-11-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

adopted 17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

adopted 17 December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

- Storage: 2 to 8 °C, protected from light, under nitrogen
- Batch Number: Ln11013894
- Retest Date : 31 July 2019
- Purity: 100%
- Appearance:brown viscous liquid


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Dose levels were expressed gravimetrically and in terms of test article received (without regard to purity or active content). The test article was prepared in corn oil. The formulated concentrations were calculated from the selected dose level and the dose volume of 10 mL/kg. All formulations were used within two hours of preparation. Dose containers were repeatedly inverted prior to administration to ensure homogeneity.

Species:

rat

Strain:

other: Female (nulliparous, non-pregnant) Crl:WI(Han) strain rats

Sex:

female

Details on test animals or test system and environmental conditions:

- Environmental Conditions, Diet, Water and Bedding
The animals were kept in the following conditions except for short periods of time where experimental procedures dictated otherwise.
- Housing
The animals were housed in groups of up to five in cages that conformed to the 'Code of Practice for the Housing and Care of Animals Bred, Supplied or Used for Scientific Purposes’ (Home Office, London, 2014).
Bedding was provided on a weekly basis to each cage by use of clean European soft wood bedding (Datesand Ltd., Manchester, UK). The bedding had been analysed for specific contaminants.
No contaminants were present in bedding at levels which might have interfered with achieving the objective of the study. Results are retained on file at Covance.
- Water
Mains water was provided ad libitum via water bottles. The water was periodically analysed for specific contaminants.
No contaminants were present in water at levels which might have interfered with achieving the objective of the study. Results are retained on file at Covance.
- Diet
Throughout the study the animals had access to 5LF2 EU Rodent Diet 14%, which was freely available to the animals at all times, except for a period of fasting from the evening of the day prior to dosing (Day-1) until approximately 3 hours after dosing. Each batch of diet had been analysed for specific constituents and contaminants by the manufacturer.
No contaminants were present in diet at levels which might have interfered with achieving the objective of the study. Results are retained on file at Covance.
- Environment
The animal rooms were designed to permit 15 to 20 air changes per hour. The target temperature and humidity ranges were 20 to 24 Deg C and 45 to 65% respectively. Daily recordings of maximum and minimum temperature and humidity were made.
Fluorescent lighting was controlled automatically to give a cycle of 12 hours light and 12 hours dark.
- Environmental Enrichment
In order to enrich both the environment and the welfare of the animals, they were provided with wooden Aspen chew blocks and rodent retreats.
Environmental enrichment materials were removed during the period of fasting.
- Animal Identification
A number written on the tail in indelible ink on the day before dosing individually identified the rats. A colour-coded card on each cage gave information including study number, group number, animal numbers and sex.

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

In the preliminary study a female fasted rat was given the test article as a single dose on Day 1 by oral gavage at a dose level of 300 mg/kg. As no deaths were observed at this dose, a subsequent dose of 2000 mg/kg was administered to a single female fasted rat by oral gavage. The animal treated at 2000 mg/kg was humanely killed approximately 3 hours after dosing due the severity of the clinical signs. A further four female fasted rats were therefore given a single oral dose of test article at a dose level of 300 mg/kg body weight. No deaths were noted in animals treated at 300 mg/kg.

No. of animals per sex per dose:

4 females in the main study

Control animals:

no

Details on study design:

- Health Monitoring:
All animals were observed at the beginning and the end of the working day for signs of ill health or overt toxicity. Any animal which showed marked signs of ill health was isolated.
- Clinical Signs:
Treated rats were observed closely for clinical signs of reaction to treatment. Clinical signs were recorded prior to dose immediately post-dose, at approximately 15 and 30 minutes post-dose, hourly between 1 and 4 hours post-dose (inclusive), twice daily on Days 2, 3 and 4 and once daily from the fifth to last day of the observation period. Individual records of clinical signs and times of death were maintained for each treated rat.
Animals showing severe and enduring clinical signs and those considered moribund were killed by exanguination under deep isoflurane anaesthesia.
- Body Weights:
Rats were weighed on Day-1 (day before dosing) and on Days 1, 4, 8 and 15. Decedent carcass weights were also recorded prior to necropsy.
- Necropsy:
Rats surviving treatment were killed on Day 15. Each animal was given isoflurane anaesthesia. Once a suitable deep plane of anaesthesia had been established, the animal was exsanguinated by the severing of major blood vessels. After exsanguination a full macroscopic necropsy was performed and all lesions were recorded. The necropsy procedure included inspection of external surfaces and orifices, all viscera and tissue within the abdominal, thoracic and cranial cavities, free-hand sectioning of the liver and kidneys and examination of representative sections of mucosal surfaces of the stomach, small and large intestines.
Animals dying during the observation period were subject to a similar necropsy with the least possible delay. Carcasses were stored in a refrigerator until necropsy commenced.
- Preservation of Tissues for Histopathology:
Representative samples of macroscopic changes found at necropsy were retained in 10% neutral buffered. However, the Sponsor confirmed that microscopic examination was not required.

Preliminary study:

In the preliminary study a female rat was given the test article as a single dose on Day 1 by oral gavage at a dose level of 300 mg/kg. As no deaths were observed at this dose, a subsequent dose of 2000 mg/kg was administered to a single female fasted rat by oral gavage.
The animal treated at 2000 mg/kg was humanely killed approximately 3 hours after dosing due the severity of the clinical signs. A further four female fasted rats were therefore given a single oral dose of test article at a dose level of 300 mg/kg body weight. No deaths were noted in animals treated at 300 mg/kg.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No deaths were noted in animals treated at 300 mg/kg. No clinical signs were seen in animals treated at 300 mg/kg.

Mortality:

No deaths were noted in animals treated at 300 mg/kg. The animal treated at 2000 mg/kg was humanely killed approximately 3 hours after dosing due to the severity of the clinical signs.

Clinical signs:

other: No clinical signs were seen in animals treated at 300 mg/kg. Clinical signs noted in the animal treated at 2000 mg/kg were ataxia, decreased activity, laboured breathing, hypothermia, prone posture and loss of righting reflex. The clinical signs developed

Gross pathology:

The only abnormality noted at necropsy of the animal that was killed in extremis was dark contents in the stomach. nNo abnormalities were noted at necropsy of animals killed at the end of the study.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The test article was classified as Category 4 in respect of its acute oral toxicity according to CLP Regulation 1272/2008.

Executive summary:

In an acute oral toxicity study conducted according to OECD guideline 420, groups of fasted female rats were given Neodecanoic acid, iron salt (100% purity) as a single oral dose in corn oil. In a preliminary study, a female rat was given the test article as a single dose at a dose level of 300 mg/kg bw. As no deaths were observed, a subsequent dose of 2000 mg/kg bw was administered to a further single female by oral gavage. The animal treated at 2000 mg/kg was humanely killed approximately 3 hours after dosing due to severity of the clinical signs. A further four female rats were therefore given a single oral dose of 300 mg/kg bw. No mortality occurred and no clinical signs were recorded. All surviving rats gained weight during the first and second weeks of the 14-day observation period. No abnormalities were noted at necropsy of animals killed at the end of the study. Based on the result, the LD50 is greater than 300, but lower than 2000 mg/kg bw. Thus, classification as Acute Tox 4, H302 is warranted in accordance with CLP Regulation 1272/2008.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

300 mg/kg bw

Quality of whole database:

GLP study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

supporting study

Justification for type of information:

For details and justification of read-across please refer to the attached report in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

not specified

Dose descriptor:

LC0

Effect level:

other: saturated atmosphere of aerosol generated from 40% aqueous solution of iron chloride

Based on:

test mat.

Exp. duration:

8 h

Mortality:

No mortality observed

Interpretation of results:

study cannot be used for classification

Conclusions:

No mortalities were observed in rats following an 8 hour exposure to a saturated atmosphere of aerosol generated from a 40% aqueous solution of ferric chloride

Executive summary:

This information is used in a read-across approach in the assessment of the target substance.For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Sex:

male

Dose descriptor:

LC50

Effect level:

> 3 mg/L air (nominal)

Exp. duration:

6 h

Remarks on result:

other: mice and rats

Sex:

male

Dose descriptor:

LC50

Effect level:

< 3 mg/L air (nominal)

Exp. duration:

6 h

Remarks on result:

other: guinea pig

Mortality:

2 guinea pigs died on the 2nd day, 1 on the 13th, and 2 on the 14th post exposure.
All mice and rats survived.

Clinical signs:

other: No significant signs of respiratory irritation were noted. Alopecia and some weight loss were noted in the guinea pigs during the 14-day observation period.

Body weight:

Not analyzed.

Gross pathology:

No significant findings.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results from an acute inhalation study conducted similar to OECD 403 in rats, mice and guinea pigs, the LC50 for neodecanoic acid can be considered to >3 mg/L for mice and rats.

Executive summary:

Neodecanoic acid was administered via vapor inhalation to 10 male animals of each species (mice, rats, and guinea pigs) at the nominal concentration of 3 mg/l for 6 hours. Clinical observations were made every 30 minutes during the exposure and daily thereafter for 14 days. No significant signs of respiratory irritation were noted.  Alopecia and some weight loss were noted in the guinea pigs during the 14-day observation period.  Two guinea pigs died on the 2nd day, 1 on the 13th, and 2 on the 14th post exposure.  All mice and rats survived.  Based on these data it is concluded that the LC50 for mice and rats is greater than 3 mg/L.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

 

Reference 3

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 511 mg/m³ air

Exp. duration:

6 h

Remarks on result:

other: all species

Mortality:

1 female guinea pig from the control group on Day 5 post exposure.

Clinical signs:

other: Group 1 (Control) - No adverse effects Group 2 (Treated) - During exposure some mice exhibited labored breathing and partially closed eyes. Some rats, showed slight amounts of salivation. All guinea pigs and the other mice and rats appeared to be normal.

Body weight:

Group 1 (Control) - No adverse effects
Group 2 (Treated) - No adverse effects

Gross pathology:

Group 1 (Control) - No adverse effects
Group 2 (Treated) - All mice were free of any abnormalities. Rats exhibited kidney abnormalities consisting of discoloration, dilated renal pelvis, and a flaccid appearance. Rats also exhibited lung discoloration and liver congestion. Guinea pigs displayed lung discoloration.

Interpretation of results:

GHS criteria not met

Conclusions:

The LC50 for neodecanoic acid is greater than 511 mg/m³.

Executive summary:

In this acute inhalation toxicity study (equivalent to OECD 403), groups of 10 mice, rats, and guinea pigs/sex were exposed whole body to an aerosol of neodecanoic acid at a concentration of 511 mg/m³ for 6 hours followed by a 14 day post exposure observation period. A control group was exposed to room air only. During the exposure some mice exhibited labored breathing and partially closed eyes, and some rats, showed slight amounts of salivation. All the guinea pigs and the other mice and rats appeared to be normal. Upon removal from the chamber all the mice and most of the guinea pigs exhibited material on their fur. The rats displayed red staining around the nasal area, anogenital staining, soft stool, salivation, and lacrimation. Necropsy revealed all mice were free of any abnormalities. Rats exhibited kidney abnormalities consisting of discoloration, dilated renal pelvis, and a flaccid appearance. Rats also exhibited lung discoloration and liver congestion. Guinea pigs displayed lung discoloration. It is concluded that the LC50 is greater than 511 mg/m³.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the attached report in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

During the study, there was no unscheduled death.

Clinical signs:

other: Yellowish-brown change on the skin of applied site was observed in all treated animals from day 2 but this sign was recorvered on day 15 except 3 animals. 2 males and 4 females showed the reddish nasal discharge on day 2.

Gross pathology:

Internally, no abnormalities were observed in all animals by microscopic examination. On application sites, scars were observed in one male and one female.

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results, the LD50 value for iron dichloride was determined to be greater than 2000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study conducted according to OECD guideline 402, groups of Sprague-Dawley rats (5/sex) were treated dermally for 24 hours with 2000 mg/kg bw iron dichloride (98.5% purity). No mortality occurred during the 14-day observation period. Yellowish-brown changes on the skin of applied sites were observed in all treated animals from day 2 but this was recovered during the test period, except for 3 females. 2 males and 4 females showed reddish nasal discharge on day 2. All rats gained normal body weight throughout the study. Regarding gross pathology, no abnormalities were observed in all animals. Only in one male and in one female, scars were observed on the application sites. Based on the results, the dermal LD50 can be considered to be greater than 2000 mg/kg bw (

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 13.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 160 mg/kg bw

Remarks on result:

other: All animals survived.

Mortality:

All animals survived.

Clinical signs:

other: No irritation was seen at 50 mg/kg; minimal irritation consisting of slight erythema, atonia, and desquamation which completely subsided in 10 days was noted at the 200 mg/kg level. More pronounced dose-related irritation was seen at the higher levels an

Gross pathology:

No significant findings.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 for neodecanoic acid is greater than 3160 mg/kg.

Executive summary:

In this acute dermal toxicity study (similar to OECD 402), groups of 8 rabbits/sex were exposed to undiluted neodecanoic acid at doses of 50, 200, 794, 3160 mg/kg via an occluded dermal patch for 24 hours.  Clinical assessments were performed at 1, 4 and 24 hours and once daily thereafter for 14 days post exposure.  No irritation was seen in the 50 mg/kg dose group; minimal irritation consisting of slight erythema, atonia, and desquamation which completely subsided in 10 days was noted at the 200 mg/kg level.  More pronounced dose-related irritation was seen at the higher levels and consisted of slight to moderate erythema which disappeared after the fourth and eighth days, and slight to moderate atonia and desquamation which persisted in diminishing severity through the 14-day observation period.  All animals survived the exposure.  Based on these data, the LD50 is greater than 3160 mg/kg.

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

Reference 3

Endpoint:

acute toxicity: dermal

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Justification for type of information:

For details and justification of read-across please refer to the report attached in section 13 of IUCLID.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 640 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No animals died

Mortality:

No animals died

Clinical signs:

other: No adverse effects noted

Gross pathology:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal LD50 for neodecanoic acid is greater than 3640 mg/kg bw.

Executive summary:

In this acute dermal toxicity study conducted similar to OECD 402, groups of two Wistar rats/sex were dermally exposed to 4 mL/kg bw (equals 3640 mg/kg bw) neodecanoic acid via an occluded dermal patch for 24 hours. After 24 hours, the patch was removed and clinical observations were made once daily for 9 days. There were no deaths observed in this study and there were no signs of toxicity. It is concluded that the dermal LD50 is greater than 3640 mg/kg bw. 

This information is used in a read-across approach in the assessment of the target substance. For justification of read-across please refer to the attached read-across report (see IUCLID section 13).

 

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

For the oral route, suitable test data is available for the target substance Neodecanoic acid, iron salt. In an acute oral toxicity study conducted according to OECD 420, one animal treated at 2000 mg/kg bw was humanely killed approximately 3 hours after dosing due the severity of the clinical signs. A further four female rats received as a second step a single oral dose of 300 mg/kg bw. No deaths were noted in animals treated at 300 mg/kg bw. Therefore, the LD50 is >300 and < 2000 mg/kg bw.

For the dermal and inhalation route, no data is available for the target substance. Thus, available data from Neodecanoic acid, Iron dichloride and Iron trichloride were used in a read-across approach to assess the acute toxicity via the dermal and inhalation route of the target substance. For details and justification of read-across please refer to the attached report in section 13 of IUCLID. In the available read-across data, no read-across substance has shown any acute toxicity for the exposure route tested.

In conclusion, based on the available data, the target substance is not acutely toxic via the dermal and inhalation route, but classification as Acute Tox. 4, H302 for the oral route is warranted.

Justification for classification or non-classification

In conclusion, based on the available data, the target substance is not acutely toxic via the dermal and inhalation route, but classification as Acute Tox. 4, H302 for the oral route is warranted in accordance with CLP Regulation 1272/2008.