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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

In an acute oral toxicity study (reliability score 2), conducted to a protocol similar to the now deleted OECD Test Guideline 401 and pre-GLP, HEDP (2-3Na) was administered by oral gavage to female rats. An LD50 of 3550 mg/kg bw which is equivalent to 2925 mg/kg bw active acid was concluded (Henkel KGaA, 1984).

 

In an acute dermal toxicity study (reliability score 2), conducted prior to the adoption of OECD test guidelines and pre-GLP, the LD50 for HEDP (2-3Na) was >7940 mg/kg bw in rabbits. This was based on no observed mortality although some toxicity was observed including reduced appetite and activity for one to three days (Younger lab, 1971).

No data for acute inhalation toxicity are available.

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:
1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source:
- Females nulliparous and non-pregnant: Not specified
- Rationale for use of males: N/a
- Age at study initiation: Not specified
- Weight at study initiation: Not specified
- Fasting period before study: Not specified
- Housing: Animals were kept in 3 Makrolon cages, individually housed.
- Historical data: Not specified
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: Not specified
- Microbiological status when known : Not specified
- Method of randomisation in assigning animals to test and control groups

ENVIRONMENTAL CONDITIONS
- Temperature (°C): As recommended in the guideline
- Humidity (%): As recommended in the guideline
- Air changes (per hr): As recommended in the guideline
- Photoperiod (hrs dark / hrs light): As recommended in the guideline

IN-LIFE DATES: Not specified
Route of administration:
oral: gavage
Vehicle:
water
Doses:
2510, 3160, 3570, 3980 mg/kg at 20ml/kg
No. of animals per sex per dose:
10 females in total
Control animals:
no
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
3 550 mg/kg bw
Remarks on result:
other: equivalent to 2925 mg/kg bw/day active acid
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study, conducted to a protocol similar to the now deleted OECD Test Guideline 401 and pre-GLP, HEDP (2-3Na) was administered by oral gavage to female rats. An LD50 of 3550mg/kg which is equivalent to 2925 mg/kg bw/day active acid was concluded.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 925 mg/kg bw
Quality of whole database:
(active acid)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Study conducted prior to the adoption OECD test guidelines.
Deviations:
yes
Remarks:
Only one animal tested and limited reporting.
GLP compliance:
no
Remarks:
pre-GLP
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
water
Duration of exposure:
At least 24 hours.
Doses:
2000, 3160, 5010, 7940 and 7940 mg/kg bw (the report gives the highest dose twice, it is assumed that the duplicated dose is the highest dose).
No. of animals per sex per dose:
One (male or female)
Control animals:
not required
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 940 mg/kg bw
Remarks on result:
other: No deaths.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study (reliability 2), conducted prior to the adoption of OECD test guidelines and pre-GLP, the LD50 for HEDP (2-3Na) (25% aqueous solution) was >7940 mg/kg bw in rabbits. This was based on no observed mortality although some toxicity was observed including reduced appetite and activity for one to three days.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 7 940 mg/kg bw
Quality of whole database:
(active acid)

Additional information

In an acute oral toxicity study (reliability score 2), conducted to a protocol similar to the now deleted OECD Test Guideline 401 and pre-GLP, HEDP (2-3Na) was administered by oral gavage to ten female Wistar rats in concentrations of 2510, 3160, 3570, 3980 mg/kg bw at 20 mL/kg using water as the vehicle. The animals were individually housed and kept in three Makrolon cages. An LD50 of 3550 mg/kg bw which is equivalent to 2925 mg/kg bw active acid was concluded (Henkel KGaA, 1984).

In an acute oral study (reliability score 2), conducted using a protocol similar to the now deleted OECD Test Guideline 401 but pre-GLP, undiluted HEDP-4Na was administered to five Sprague-Dawley rats by oral gavage in a limit test. Within seven hours, all of the animals had died. Therefore, a range-finding study and subsequently, an LD50 was determined. In the range-finding study, doses of 50, 100, 500, 1000 or 2000 mg/kg bw were administered to one male and one female Sprague-Dawley rat. Based on the findings of this study, doses of 2000, 2500, 3200 and 4000 mg/kg bw HEDP-4Na was administered to five male and five female Sprague-Dawley rats by oral gavage. Animals were observed for 14 days following dosing, and all animals were examined macroscopically. Body weights were recorded prior to dosing and on days 7 and 14. Mortality was observed in 1, 4, 7 and 8 animals, respectively. Observations in all groups for up to four hours post-dosing, included ataxia and/or tremors, oral and nasal discharge, hypoactivity, soft stool and faecal and/or urinary staining. The majority of surviving animals showed some weight loss during the first week after dosing, although all animals gained weight between days 7 and 14. Macroscopic abnormalities observed at necropsy were primarily changes to the lungs (discolouration) and gastrointestinal tract (red or black walls, or red or black fluid present, suggestive of an irritant effect). Most of the animals in the 2500, 3200 or 4000 mg/kg dose groups had enlarged kidneys at necropsy and one animal in the 4000 mg/kg bw group had unilateral renal pallor, dilated renal pelvis and red fluid surrounding the kidney. The LD50 was calculated to be 2850 mg/kg bw (equivalent to 940 mg/kg/day bw active salt and 659 mg/kg bw/day active acid) (BioDynamics Inc., 1985).

 

In a well conducted acute oral toxicity study (reliability score 2), conducted using a protocol similar to the now deleted OECD Test Guideline 401 but pre-GLP, a concluded LD50 of 5300 mg/kg bw (presumed to be equivalent to 3715 mg active acid/kg bw and 1219 mg active salt/kg bw) were determined in rats for HEDP-4Na. This was based on mortality occurring in two of five rats at 5300 mg/kg bw as well as some toxicity including diarrhoea, convulsions and rapid weakness with collapse in 10-30 minutes post-dosing. Some of the animals that collapsed improved within 1-2 hours and survived (Younger Laboratories, 1965).

In an acute oral toxicity study (reliability score 2), unknown if in accordance with any OECD Test Guideline and pre-GLP, an LD50 of 1340 mg/kg, equivalent to 1104 mg/kg bw active acid was determined for the 25 % active ingredient of HEDP (2-3Na) in the rat (Nixon et al., 1972).

In a well conducted acute oral toxicity study (reliability score 2), conducted using a protocol similar to the now deleted OECD 401 but pre-GLP, an LD50 of 3400 mg/kg bw was determined for HEDP (2-3Na) in the rat (Younger Lab, 1971).

In an acute oral toxicity study (reliability score 2), unknown if comparable to any OECD Test Guidelines and pre-GLP, HEDP (2-3Na) was tested in various gavage doses in male (immature and mature) and female (immature, mature, pregnant and non-pregnant) New Zealand white rabbits. The lowest LD50 found for mature male rabbits was 581 mg/kg bw (equivalent to 139.4 mg/kg bw/day active acid) while younger (immature) animals appeared less sensitive with an LD50 of 1140 mg/kg bw (equivalent to 939.4 mg/kg bw/day active acid) (Nixon et al., 1968).

In a supporting acute oral toxicity (reliability score 4), prior to the adaptation of OECD Test Guideline and pre-GLP, the LD50 in mice for HEDP (2-3Na) is 3300 mg/kg bw, equivalent to 2719 mg/kg bw/day active acid (Gloxhuber, 1969).

 

In a series of supporting acute oral toxicity studies (reliability score 4), not conducted according to any OECD Test Guideline and pre-GLP, LD50s are determined to be 1300 mg/kg bw in rats; 1100 mg/kg bw in rabbits and approximately (part of dose vomited) 1000 mg/kg bw dogs for HEDP (2-3Na) Henkel KGaA, 1978).

In an acute oral toxicity study (reliability score 4), conducted prior to the adaptation to OECD Test Guidelines and pre-GLP, the LD50 for HEDP (2-3Na) in mice was greater than 5000 mg/kg bw which is equivalent to 4120 mg/kg bw/day active acid (Henkel KGaA, 1975).

In an acute oral toxicity study, available only as a summary (reliability score 4) and pre-GLP, the LD50 for HEDP (2 -3Na) was >5000 mg/kg bw in mice (Potokar, 1974).

In an acute oral toxicity study (reliability score 4), conducted using a protocol similar to the now deleted OECD 401 but unknown if in compliance with GLP, the LD50 for HEDP (2-3Na) was 10896 mg/kg bw (9807 – 12107 mg/kg) for female rats and 12983 mg/kg bw (12467 – 13522 mg/kg) for male rats (Landmann, 1987).

In a non-standard acute toxicity study (reliability score 4), not conducted according to any OECD Test Guideline and pre-GLP, HEDP (2-3Na) did not produce any effects on clinical chemistry compared to HEDP-NaF and NaF, after a single oral dose of 3.3 ppm in rats (Bartnik, 1981).

In an acute oral toxicity study (reliability score 4), not conducted according to any OECD Test Guideline and pre-GLP, HEDP (2 -3Na) was administered to mouse by oral gavage. An LD50 value of 3300mg/kg bw, equivalent to 2719 mg/kg bw/day active acid, was concluded in the summary report (Henkel, 1969).

In an acute dermal toxicity study (reliability score 2), conducted prior to the adoption of OECD test guidelines and pre-GLP, male and female New Zealand rabbits were exposed to HEDP (2-3Na) for at least 24 hours under occlusive coverage in concentrations of 2000, 3160, 5010 or 7940 mg/kg bw. The LD50 for HEDP (2-3Na) was concluded to be >7940 mg/kg bw. This was based on no observed mortality although some toxicity was observed including reduced appetite and activity for one to three days (Younger lab, 1971).

In a well-conducted acute dermal toxicity limit test (reliability score 2), conducted according to a protocol similar to OECD Test Guideline 402 and pre-GLP, 5000 mg/kg bw of HEDP-4Na was applied to the skin of New Zealand white rabbits (5 per sex) under an occlusive dressing for 24 hours. After the 24-hour exposure period, excess test substance was wiped off the test site. Animals were observed for 14 days for signs of toxicity. Body weights were measured prior to dosing and on days 7 and 14. All animals were examined macroscopically. One female died on Day 13. However, macroscopic examination revealed signs of intestinal disease that was not considered to be related to the test substance. All other animals survived to the end of the observation period. In all surviving animals, there were some occurrences of oral and nasal discharge. Most animals had severe dermal effects at the dose site (necrosis followed by eschar formation and/or exfoliation of the eschar tissue) which persisted throughout the observation period. Most animals had slight weight losses at Days 7 and/or 14. The female that was found dead had gross abnormalities suggestive of mucoid enteritis. Apart from the presence of dermal lesions, no abnormal findings were observed in the other animals. The LD50 was determined to be >5000 mg/kg bw (BioDynamics In., 1985).

In an acute dermal toxicity study (reliability score 4), conducted prior to the adoption of OECD test guidelines and pre-GLP, the LD50 for HEDP-4Na was concluded to be >10000 mg/kg bw (presumed equivalent to >2300 mg active salt/kg bw and 7010 mg/kg bw active acid in rabbits (Younger labs, 1965).

Justification for classification or non-classification

Based on the available data for HEDP (2-3Na), HEDP (2 -3Na) is not classified for acute toxicity via any route according to Regulation (EC) No 1272/2008.